CancerMPact 2023 TA US Prostate v1.1

CancerMPact® Treatment Architecture
Prostate Cancer, U.S.

v1.1
Published September 2023

Based on fieldwork conducted
June 2023
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Table of Contents (i)
Definitions and Standard Abbreviations of Systemic Therapies 4 Role of Observation 35

Publication History 5 Role of Active Surveillance 36
Executive Summary 7 Role of Each Modality: Surgery, Radiation, Systemic Therapy 37
Temporal Trends: 2023 vs. 2022 U.S. Findings 8 Role of Surgery 39
Summary of Observed Treatment Shifts in 2023 13 Role of Radiation 40
Treatment Algorithms 14 Role of Systemic Therapy 41
Prostate Cancer Overview 22 Regulatory Approval Timeline 42
Disease Overview 23 Approved Branded Systemic Agents 43
Pathology 24 Dosing / Administration of Common Regimens 50
Diagnosis 25 Treatment: Non-Metastatic Hormone Sensitive Prostate Cancer (Stages I-IV M0) 54
Staging and Subtypes 26 Initial Treatment by Modality 55
Risk Stratification 27 Types of Radiotherapy Utilized 56
Role of Biomarkers 28 Clinical Trial Benchmarks: nmHSPC 57
Biomarker Testing Rates for mHSPC 29 Regimen Utilization for Newly Diagnosed 62
NGS Testing Rates for mHSPC 30 Time to First Recurrence 63
Biomarker Testing Rates for mCRPC 31 Stage, Location, and Hormone Sensitivity of First Recurrence 64
NGS Testing Rates for mCRPC 32 Treatment Modality for First Recurrence 65
Overview of Treatment Approaches 33 Regimen Utilization for First Recurrence 66
Role of Each Modality: Observation, Active Surveillance 34 Time to Second Recurrence 67
CancerMPact® Treatment Architecture U.S., Prostate Cancer 2

Table of Contents (ii)
Treatment: Non-Metastatic Hormone Sensitive Prostate Cancer (Stages I-IV M0) 54 Clinical Trial Benchmarks: 1L 94
Stage, Location, and Hormone Sensitivity of Second Recurrence 68 Regimen Utilization for 1L Therapy 100
Treatment Modality for Second Recurrence 69 Clinical Trial Benchmarks: Relapsed mCRPC 101
Regimen Utilization for Second Recurrence 70 Regimen Utilization: 2L 106
Treatment: Non-Metastatic Castration Resistant Prostate Cancer 71 Sequence of 1L and 2L Therapy 107
Initial Treatment by Modality 72 Regimen Utilization: 3L and 4L 108
Clinical Trial Benchmarks: nmCRPC 73 Line of Therapy Progression: mCRPC 109
Regimen Utilization for Initial Therapy 76 Outcomes of Therapy: mCRPC 110
Disease Recurrence Patterns After Initial Therapy 77 Appendix 111
Treatment: Metastatic Hormone Sensitive Prostate Cancer 78 Global Trend Comparisons 111
Initial Treatment by Modality 79 Abbreviations Used in This Report 122
Clinical Trial Benchmarks: mHSPC 80 Survey Respondent Demographics 125
Regimen Utilization for Initial Therapy 88 Full Data Tables 128
Regimen Utilization for 2L Therapy 89 References 187
Line of Therapy Progression: mHSPC 90 Cerner Enviza Contact Details 196
Outcomes of Therapy: mHSPC 91
Treatment: mCRPC 92
Initial Treatment by Modality 93

Return to Table of Contents
Definition of hormone therapies / androgen pathway disruptors used in this report
Terminology for various classes of androgen pathway disruptors used to treat both hormone-sensitive / castrate-sensitive and castrate-resistant
disease are not always consistent between regions and between different stakeholders. For the purpose of these reports, Treatment Architecture
has classified the agents in the follow manner for simplicity in charting and data insights.
Abbreviation Specific Agents Mechanism of action

A general term used to describe androgen deprivation therapy
ADT Depending on the context, ADT could refer to patients that underwent surgical castration, or may be referring to LHRH therapy with or
without first-gen ARIs, or any kind of anti-androgen including second-gen ARIs (this last case is particularly common when referring to
combinations with docetaxel)
LHRH agonists: leuprolide, goserelin, triptorelin

LHRH only LHRH antagonists: relugolix, degarelix
LHRH agonists or antagonists
First-gen ARI Androgen receptor inhibitors: flutamide, bicalutamide, nilutamide First-generation androgen receptor inhibitors
Second-generation androgen receptor inhibitors, or non-

Androgen receptor inhibitors: apalutamide, darolutamide, enzalutamide
Second-gen ARI CYP17A1 inhibitor: abiraterone acetate*
hormonal anti-androgens (NHA) and CYP17A1 inhibitor
(abiraterone acetate)
*For simplicity, abiraterone acetate (branded or generic) in combination with prednisone will be listed as abiraterone in charts and referred to as abiraterone within the text.

Publication History
The data reported in this document were originally published on September 29, 2023, based on fieldwork conducted in June 2023.
Minor updates to this module may have occurred since the original publication. If so, these dates and changes are summarized here:
Date Change
Sept 29, 2023 Original publication
Oct 31, 2021 v1.1: Title text update to slide 31

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Executive
Summary
Executive Summary Return to Table of Contents
United States 2022 United States 2023

Annual Incidence1: 259,245 Annual Incidence1: 264,037
Rank among all cancers1: 2 Rank among all cancers1: 2
Initial Treatment Modality Distribution nmHSPC2 (%) Initial Treatment Modality Distribution nmHSPC2 (%)
Stage I Stage I
Stage II Stage II
Stage III Stage III
Stage IV(M0) Stage IV(M0)
0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100%
No therapy/Observation Active Surveillance Surgery No therapy/Observation Active Surveillance Surgery
RT Systemic therapy ± Surgery Surgery, RT RT Systemic therapy ± Surgery Surgery, RT
Systemic therapy, RT Others Systemic therapy, RT Others
Top 3 Initial Systemic Therapies for nmHSPC3 Top 3 Initial Systemic Therapies for nmHSPC3
leuprolide leuprolide
Stage I bicalutamide, leuprolide Stage I enzalutamide, leuprolide
enzalutamide, leuprolide bicalutamide, leuprolide
Stage II bicalutamide, leuprolide Stage II bicalutamide, leuprolide
enzalutamide, leuprolide enzalutamide, leuprolide
Stage III enzalutamide, leuprolide Stage III enzalutamide, leuprolide
bicalutamide, leuprolide bicalutamide, leuprolide
Stage IV (M0) leuprolide Stage IV (M0) leuprolide
abiraterone, prednisone, leuprolide abiraterone, prednisone, leuprolide
1. Based on CancerMPact® Patient Metrics, accessed in March 2023. Ranking is based on relative incidence of 31 tumors in the
U.S. 2. All data are based on physician survey, as detailed in this report and other regional reports. 3. Top three regimens are listed CancerMPact® Treatment Architecture U.S., Prostate Cancer 8
unless top one or two regimens account for >70% of the utilization. Top regimen is bolded if it is at least twice as frequent as the
second in rank.

First Recurrence Treatment Modality Distribution nmHSPC2 (%) First Recurrence Treatment Modality Distribution nmHSPC2 (%)
Post Definitive Radiotherapy Post Definitive Radiotherapy
Post-Surgery Post-Surgery
Post Systemic Therapy Post Systemic Therapy
0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100%

Top 3 First Recurrence Systemic Therapies for nmHSPC3 Top 3 First Recurrence Systemic Therapies for nmHSPC3
Stage I-III enzalutamide, leuprolide Stage I-III enzalutamide, leuprolide
abiraterone, prednisone, leuprolide bicalutamide, leuprolide
Stage IV Stage IV
leuprolide abiraterone, prednisone, leuprolide
(M0) (M0) bicalutamide, leuprolide
abiraterone, prednisone, leuprolide
second in rank.

Initial Treatment Modality Distribution for Newly-Recurrent Initial Treatment Modality Distribution for Newly-Recurrent
nmCRPC Patients2 (%) nmCRPC Patients2 (%)
nmCRPC nmCRPC
0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100%
No therapy/Observation Active Surveillance No therapy/Observation Active Surveillance

Surgery RT Surgery RT
Systemic therapy ± Surgery Surgery, RT Systemic therapy ± Surgery Surgery, RT
Top 3 Newly-Recurrent Systemic Therapies for nmCRPC3 Top 3 Newly-Recurrent Systemic Therapies for nmCRPC3
enzalutamide enzalutamide
nmCRPC nmCRPC
apalutamide abiraterone, prednisone
abiraterone, prednisone darolutamide
second in rank.

Initial Treatment Modality Distribution for mHSPC Patients2 (%) Initial Treatment Modality Distribution for mHSPC Patients2 (%)
mHSPC mHSPC
0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100%
Systemic therapy ± Surgery Systemic therapy, RT Systemic therapy ± Surgery Systemic therapy, RT
Surgery, RT, Systemic therapy Others Surgery, RT, Systemic therapy Others
Top 3 Systemic Therapies for mHSPC2,3 Top 3 Systemic Therapies for mHSPC2,3
Initial therapy enzalutamide, leuprolide enzalutamide, leuprolide

Initial therapy
abiraterone, prednisone, leuprolide abiraterone, prednisone, leuprolide
for mHSPC for mHSPC
apalutamide, leuprolide apalutamide, leuprolide
abiraterone, prednisone, leuprolide enzalutamide, leuprolide

Second-line for Second-line for
enzalutamide, leuprolide abiraterone, prednisone, leuprolide
mHSPC apalutamide, leuprolide mHSPC apalutamide, leuprolide
U.S. 2. All data are based on physician survey, as detailed in this report and other regional reports. In 2022, modality and regimens CancerMPact® Treatment Architecture U.S., Prostate Cancer 11
questions were asked for mHSPC only. 3. Top three regimens are listed unless top one or two regimens account for >70% of the
utilization. Top regimen is bolded if it is at least twice as frequent as the second in rank.

mCRPC Patients2 (%) mCRPC Patients2 (%)
Asymptomatic Asymptomatic
Symtpomatic Symtpomatic
0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100%
Top 3 Systemic Therapies for mCRPC3 Top 3 Systemic Therapies for mCRPC3
Asymptomatic Symptomatic Asymptomatic Symptomatic
Initial therapy for Initial therapy for
mCRPC enzalutamide enzalutamide mCRPC enzalutamide enzalutamide
abiraterone, prednisone abiraterone, prednisone abiraterone, prednisone abiraterone, prednisone
docetaxel, prednisone docetaxel docetaxel docetaxel
Second-line for abiraterone, prednisone Second-line for abiraterone, prednisone

mCRPC enzalutamide mCRPC cabazitaxel, steroid
docetaxel docetaxel
cabazitaxel, steroid docetaxel

Third-line for Third-line for
docetaxel cabazitaxel, steroid
mCRPC mCRPC
lutetium Lu 177 vipivotide tetraxetan lutetium Lu 177 vipivotide tetraxetan
second in rank.
Executive Summary
Summary of observed treatment shifts in 2023
Shifts in treatment this year compared to the prior year. Comparison across global markets.
Look also for this symbol throughout this report. Look also for this symbol throughout this report.
Non-Metastatic Hormone Sensitive (Stages I–IV [M0]) Non-Metastatic Hormone Sensitive (Stages I–IV [M0])
• Leuprolide, either alone or in combination with enzalutamide, remains + LHRHs remains the standard-of-care for the treatment of newly diagnosed
preferred in this setting. Use of second-generation ARIs increases in more nmHSPC, either alone or in combination with a first- or second-generation
advanced stage nmHSPC. ARI. Use of second-generation ARIs (abiraterone, enzalutamide) is more
common in the U.S. and EU.
Non-Metastatic Castration-Resistant
Non-Metastatic Castration-Resistant
Treatment trends remain consistent, with over 80% of nmCRPC patients
+ Second-generation ARI use is common across regions, although agent
receiving a second-gen ARI for initial systemic therapy. U.S. physicians
preference varies by region.
report a strong preference for enzalutamide in this setting.
Metastatic Hormone Sensitive (Stage IV [M1])
Metastatic Hormone Sensitive (Stage IV [M1])
+ Administration of second-generation anti-androgens, frequently combined
While second-gen ARIs + ADT is still the most common treatment choice, use with an LHRH analogue, are common throughout treatment for mHSPC,
of docetaxel-based regimens is increasing, likely due to the high-profile however first-generation ARIs retain some utilization in Japan and China.
ARASENS and PEACE-1 trials
Metastatic Castration-Resistant
Metastatic Castration-Resistant
+ First-line treatment is relatively similar across regions, with enzalutamide or
Second-generation anti-androgens remain the preferred choice in first line abiraterone plus prednisone preferred, though greater variability is seen in
later lines. Docetaxel-based regimens are common in China while
Use of second-generation anti-androgens is decreasing in second-line, cabazitaxel plus prednisone is more heavily used in later lines in the U.S.,
possibly due to their rising use in earlier stages of disease EU5 and JP.

Executive Summary
Jump to Discussion Section
Treatment Pathway for Stage I nmHSPC
INITIAL THERAPY OUTCOMES OF INITIAL THERAPY RECURRENCE
Biochemical recurrence
HSPC (55.1%)
Refractory
(6.6%) Biochemical recurrence
No therapy/ Surgery alone
CRPC (12.9%)
Observation (23.9%)
Relapsed <1 year
(8.5%)
(9.0%) Diagnosed local-
Newly- recurrence
Diagnosed Active Surveillance RT alone Relapsed 1 – 5 years HSPC (13.3%)
Prostate (32.7%) (18.5%) (18.4%)
Diagnosed local-
Cancer Stage I
recurrence
Active Therapy Relapsed 5 – 10 years CRPC (8.0%)
(58.8%) Systemic therapy alone (15.8%)
(4.5%) Metastatic recurrence
No recurrence ≤ 10 years HSPC (5.7%)
(50.2%)
Stage I Systemic Therapy HSPC Metastatic recurrence

CRPC (5.0%)
leuprolide 26.1%
enzalutamide, leuprolide 15.1%
bicalutamide, leuprolide 14.7%
Notes: Only top 3 active modalities are shown for initial therapy and the top 2 modalities are shown for local recurrence. Colored CancerMPact® Treatment Architecture U.S., Prostate Cancer 14
cells denote most common treatment path for patients according to survey data.
Executive Summary
Treatment Pathway for Stage II nmHSPC
HSPC (42.2%)
Refractory
No therapy/ Surgery alone
CRPC (16.1%)
Observation (29.7%)
Relapsed <1 year
(4.3%)
Newly- recurrence
Diagnosed Active Surveillance RT alone Relapsed 1 – 5 years HSPC (16.6%)
Prostate (12.6%) (24.2%) (20.9%)
Diagnosed local-
Cancer Stage II
recurrence
(83.1%) RT, Systemic therapy (22.0%)
(38.2%)
Stage II Systemic Therapy HSPC Metastatic recurrence

CRPC (5.8%)
leuprolide 37.9%
Executive Summary
Treatment Pathway for Stage III nmHSPC
HSPC (26.7%)
Refractory
No therapy/ RT, Systemic therapy
CRPC (16.0%)
Observation (26.9%)
Relapsed <1 year
(2.1%)
recurrence
Newly-Diagnosed HSPC (19.6%)
Active Surveillance Surgery alone Relapsed 1 – 5 years
Prostate Cancer
(2.6%) (18.4%) (27.4%)
Stage III Diagnosed local-
recurrence
(95.3%) RT alone (20.1%)
(25.4%)
Metastatic recurrence
Stage III Systemic Therapy HSPC
CRPC (8.9%)
leuprolide 34.2%
Executive Summary
Treatment Pathway for Stage IV (M0) nmHSPC
HSPC (13.5%)
Refractory
No therapy/ Systemic therapy alone
CRPC (15.2%)
Observation (50.6%)
Relapsed <1 year
(3.3%)
recurrence
Newly-Diagnosed RT, Systemic therapy HSPC (13.9%)
Active Surveillance Relapsed 1 – 5 years
Prostate Cancer (19.0%)
(2.4%) (34.8%)
Stage IV (M0) Diagnosed local-
recurrence
(94.3%) Surgery, RT, Systemic (17.2%)
therapy (6.8%) Metastatic recurrence
(11.4%)
Stage IV (M0) Systemic Therapy HSPC Metastatic recurrence

CRPC (19.6%)
leuprolide 16.8%
abiraterone, prednisone, leuprolide 12.7%
Executive Summary
Treatment Pathway for Newly-Recurrent nmHSPC
INITIAL THERAPY RECURRENCE
No therapy/Observation (6.2%) Systemic therapy alone (49.5%)

Post-Definitive RT
Active surveillance (6.2%) RT, Systemic therapy (10.1%)
Active therapy (87.6%) Surgery alone (10.0%)


Newly-Recurrent Diagnosed local
Post-Surgery
nmHSPC Active surveillance (6.7%) RT, Systemic therapy (32.0%) recurrence
Active therapy (87.2%) RT alone (16.2%)
Post-Systemic Active surveillance (3.5%)
therapy RT, Systemic therapy (14.2%)
Active therapy (92.4%)
RT alone (7.6%)
Stage I-III Systemic Therapy HSPC Stage IV (M0) Systemic Therapy HSPC
leuprolide 24.7% enzalutamide, leuprolide 29.0%

enzalutamide, leuprolide 20.9% abiraterone, prednisone, leuprolide 20.6%
bicalutamide, leuprolide 11.6% bicalutamide, leuprolide 12.8%
Executive Summary
Treatment Pathway for nmCRPC
Remain untreated until development of mCRPC (41.6%)
No therapy/ Refractory
Observation (12.0%)
5.1% Metastatic recurrence
Relapsed <1 year (64.3%)
Systemic therapy alone (24.7%) Initial treatment for
Newly-Developed Active Surveillance
(58.7%) mCRPC
nmCRPC 5.2%
Relapsed 1 – 5 years Local recurrence
RT, Systemic therapy (42.3%) (35.7%)
Active Therapy (10.4%)
89.7% No recurrence ≤ 5 years
Surgery, Systemic therapy (21.1%)
(6.1%)
Initial Systemic Therapy for Newly-Developed nmCRPC
enzalutamide 38.8%
abiraterone, prednisone 18.3%
darolutamide 15.3%
Executive Summary
Treatment Pathway for mHSPC
OUTCOMES OF OUTCOMES OF
INITIAL THERAPY
INITIAL THERAPY SECOND-LINE THERAPY
Systemic therapy alone Progress to CRPC (34.0%) Progress to CRPC (41.6%)

(68.3%)
Receive 2L Systemic Therapy for Receive 3L Systemic Therapy for
RT, Systemic therapy mHSPC (20.6%) mHSPC (15.1%)
mHSPC
(11.6%) Progress, remain mHSPC but Progress, remain mHSPC
untreated (14.6%) untreated (13.2%)
Surgery, Systemic therapy
(4.9%) Deceased (13.4%) Deceased (17.6%)
Long-term response (17.5%) Long-term response (12.5%)
Initial Systemic Therapy mHSPC Systemic Therapy for Second-Line mHSPC

enzalutamide, leuprolide 25.4% enzalutamide, leuprolide 20.2%
abiraterone, prednisone, leuprolide 12.9% abiraterone, prednisone, leuprolide 13.2%
apalutamide, leuprolide 8.2% apalutamide, leuprolide 8.7%
Executive Summary
Treatment Pathway for mCRPC
INITIAL THERAPY OUTCOMES OF OUTCOMES OF

INITIAL THERAPY SECOND-LINE THERAPY
Systemic therapy alone

(66.1%)
Receive 2L Systemic Therapy Receive 3L Systemic Therapy
(47.7%) (35.8%)
Newly-Developed RT, Systemic therapy
Asymptomatic (9.7%) Progress, untreated (19.5%) Progress, untreated (20.7%)
mCRPC
Surgery, Systemic therapy Deceased (18.4%) Deceased (25.8%)
(7.0%)
Long-term response (14.4%) Long-term response (17.7%)
Systemic therapy alone

(63.4%)
Receive 2L Systemic (46.6%)
Newly-Developed
RT, Systemic therapy
Symptomatic Progress, untreated (18.4%)
(13.1%)
mCRPC
Deceased (22.0%)
Surgery, Systemic therapy
(6.5%) Long-term response (13.0%)
Systemic Therapy for Newly-Developed Asymptomatic mCRPC
enzalutamide 37.9%
abiraterone, prednisone 22.9%
docetaxel 12.4%
Systemic Therapy for Newly-Developed Symptomatic mCRPC Systemic Therapy for Second-Line Systemic Therapy for Third-Line
enzalutamide 33.9% abiraterone, prednisone 13.8% docetaxel 18.3%
abiraterone, prednisone 16.4% cabazitaxel, steroid 13.7% cabazitaxel, steroid 13.4%
docetaxel 15.1% docetaxel 13.0% lutetium Lu 177 vipivotide tetraxetan 12.4%
Prostate
Cancer
Overview
Disease Overview Return to Table of Contents
Prostate cancer disease overview
Annual Incidence
Risk factors for developing prostate cancer1
264,037 Age: Prostate cancer is rare in men younger than 40. The chance of having prostate cancer rises
rapidly after age 50, and 6 in 10 cases are found in men older than 65.
Rank among all cancers (Incidence) Race / Ethnicity: Prostate cancer develops more often and at a younger age in men of African-
American and Caribbean ancestry. In contrast, prostate cancer occurs less often in men of Asian-
2 American and Hispanic / Latino descent compared to non-Hispanic whites.
Geography: Prostate cancer is most common in North America, northwestern Europe, Australia, and
the Caribbean. It is less common in Asia, Africa, Central America, and South America. Regional
Median age at diagnosis differences may be partially due to disparities in screening rates.
68 Family history: While most prostate cancers occur in men without a family history, having a father or
brother with prostate cancer more than doubles a man’s risk of developing the disease.
Genetics: Inherited mutations are associated with an increased risk of prostate cancer. These include
Male : Female Ratio mutations in BRCA1/2 and genes associated with Lynch syndrome (MLH1, PMS2, MSH2, MSH6).
1:0
Factors with less clear of an effect: Diet (increased dairy consumption), obesity, smoking, chemical
exposure, inflammation of the prostate, sexually transmitted infections, and vasectomy are all associated
with increased risk in the development of prostate cancer, though inconclusive evidence is associated with
many of these factors.
5-year Survival
Stage I-IV(M1) Stage IV (M1)
84% / 26%
Sources: Statistics from CancerMPact® Patient Metrics U.S., accessed March 2023, reported for all stages combined unless
otherwise noted. Ranking is based on relative incidence of 31 tumors. CancerMPact® Treatment Architecture U.S., Prostate Cancer 23
1. Risk factors from the American Cancer Society (www.cancer.org) and references within.
Pathology of prostate cancer
Prostate cancer is one of the most common cancers in men, occurring Prostate tumor growth rates vary from very slow to moderately rapid
primarily in men over age 65, and is a common cause of male cancer deaths and the disease may be curable when localized and sensitive to hormone
worldwide. A sharp increase in prostate cancer incidence was observed in deprivation therapy. Early-stage disease management may include
the U.S. beginning in the early 1990’s due to increased early detection based observation or active surveillance for slow growing tumors, radiation or
on prostate-specific antigen (PSA) screening. In 2008, the U.S. Preventive surgery as local therapy, or systemic androgen deprivation therapy for more
Services Task Force (USPSTF) recommended against PSA screening in advanced disease.
men over 75 to avoid overtreatment of prostate cancers that do not threaten
life expectancy. In 2012, the USPSTF recommended against routine PSA
screening for all men. As a result of these recommendations, overall prostate Disease progression ultimately leads to castration-resistant metastatic
cancer incidence declined, particularly among men older than 75, though an disease in which patients may still be responsive to systemic therapy
increased incidence of late-stage disease was observed.1-2 In 2018, the although curative options are limited. Some patients may have prolonged
USPSTF released updated recommendations for men aged 55-69, allowing survival even after their cancer has metastasized to distant sites, and many
a more balanced approached to early detection screening to include patients will die of other causes without suffering significantly from prostate
individualized decision-making and PSA testing coupled with the use of cancer due to their advanced age at diagnosis.
imaging and biomarkers to improved screening specificity and early
detection of disease.3
Ninety-five percent of prostate cancers are adenocarcinomas, which

begin as tumors on the outside of the prostate gland. Small-cell tumors,
intralobular acinar carcinomas, ductal carcinomas, clear cell carcinomas, and
mucinous carcinomas represent the remaining 5% of prostate cancers. In
general, the degree of tumor differentiation and abnormality of histologic
growth pattern directly correlate with survival.
Sources: NCCN Guidelines v3.2023 Prostate Cancer. 1. Herget, Cancer Med, 2016, 2. Negoita, Cancer, 2018, 3. The US CancerMPact® Treatment Architecture U.S., Prostate Cancer 24
Preventative Services Task Force (USPSTF)
Diagnosis of prostate cancer

“Prostate cancer represents a true spectrum of disease and not all patients diagnosed with prostate cancer require treatment… The
challenge is to minimize overtreatment of indolent cancers by accurately characterizing the biology of the detected cancer.” The NCCN
has developed guidelines to specifically address competing methods available for prostate cancer detection.1
Baseline Evaluation PSA testing and Digital Rectal Examination Biopsy3

Initial workup of both patient history and physical Prostate-specific antigen (PSA) testing is Surpassing defined PSA thresholds often prompts a
health are considered. This should include: recommended for the early detection of prostate patient to consider a prostate biopsy. NCCN Prostate
cancer in informed, healthy men ages 55-69 years on Cancer Early Detection guidelines recommend that
+ Familial cancer history
an individualized basis. Although PSA is not a cancer- men with PSA > 3 ng/mL undergo additional workup,
+ History of prostate disease and prior screening
specific marker, the risk of prostate cancer including repeat PSA and DRE (if not performed during
+ Race
increases with increasing PSA levels, and serum initial assessment) to inform decisions about whether
+ Familial genetic mutation profile
PSA levels are considered when determining clinical to proceed with biopsy. Needle biopsy and fine needle
+ Medications
stages and risk groups. Clinical guidelines recommend aspiration are equally accurate, and transrectal
+ Estimates of life expectancy
screening procedures to minimize the detection and ultrasound (TRUS) is most often used in directing
Genetic testing treatment of benign or indolent disease.1,3 needle biopsy. Pre-biopsy multiparametric magnetic
resonance imaging (MRI) should also be considered,
Germline mutation testing is recommended for While most evidence supports use of serum PSA for which is thought to better select biopsy recipients,
patients of relatives with Lynch-syndrome related early detection of prostate cancer, digital rectal identify indolent disease, and guide needle placement.
cancers and other hereditary cancer types, including examination (DRE) is recommended by many experts
breast and ovarian cancer. Germline testing is also for the early detection of prostate cancer. DRE may For disease that is deemed to be potentially
recommended for patients with a parent or sibling with detect clinically significant cancers that are missed by metastatic, pelvic lymph node dissection (PLND) is
prostate cancer ≤ 60 years old. Prostate cancer can PSA, as PSA-detected cancers are most often the most accurate method to assess metastatic
also be associated with somatic mutations. An confined to the prostate. involvement of the pelvic lymph nodes.
estimated 90% of mCRPC contain a potentially
actionable mutation.2
1. NCCN Guidelines Version 1.2023 Prostate Cancer Early Detection; 2. Robinson, Cell, 2015 3. NCCN Guidelines v3.2023 CancerMPact® Treatment Architecture U.S., Prostate Cancer 25
Prostate Cancer;
Disease Overview Jump to Table 1 and Table 2
Staging and subtypes of prostate cancer
Current Staging Distribution, Current Subtype Distribution,

The TNM (Tumor, Node, and Metastasis) staging Prostate Cancer, U.S., 2023 (Table 1)a Prostate Cancer, U.S., 2023 (Table 2)b
system by the American Joint Committee on
Cancer (AJCC, 8th Ed) is used for prostate cancer
staging of biopsy specimens. Because prostate cancer
tumors are generally slow-growing and only about 30% 26% 24% 24%
of patients with limited-stage disease will progress to
have clinically relevant disease, selection of a Stage I nmHSPC 38%
treatment plan based solely on stage is difficult. Stage II
nmCRPC
Stage III
In advanced disease, categorization of prostate mHSPC
Stage IV (M0)
cancers by hormone sensitivity is an important
Stage IV (M1) mCRPC
aspect in understanding patient risk and identifying 15% 19% 19%
relevant therapies. Men who stop responding to
traditional androgen deprivation therapies (ADT) are
considered to have castration-resistant prostate cancer 16% 18%
(CRPC). An increasing PSA level (or biochemical
recurrence) is one indicator of CRPC. A short PSA
doubling time (PSADT) is indicative of a higher risk
of mortality. The current stage distribution depicted in the pie chart is the The current subtype distribution depicted in the pie chart is the
perception of physicians who completed the Treatment perception of physicians who completed the Treatment
Architecture survey. Architecture survey.
For a population-based representation of stage at diagnosis,

please refer to the Patient Metrics module of CancerMPact.
a) QP1 (n=112): How do prostate cancer patients present in your practice? What stage of disease do patients have when they were
first diagnosed with prostate cancer? What is the staging distribution of the prostate cancer patients you currently see in your
practice? b) QP1A (n=112): What percent of your prostate cancer patients that you currently see in your practice have the following CancerMPact® Treatment Architecture U.S., Prostate Cancer 26
subtypes? Based on NCCN Guidelines v3.2023 Prostate Cancer;
Disease Overview Jump to Table 3, Table 4 and Table 5
Risk stratification of prostate cancer
Distribution of Patients by NCCN Risk Stratification,

U.S., 2023 (Table 3)a 85% ofclassified
newly diagnosed patients (and 75% of recurrent patients) are
based on NCCN Risk Stratification a
100% + NCCN guidelines incorporate a risk stratification schema accounting for

radiographically determined clinical T stage, grade, and serum PSA levels to
90%
15% assign patients to risk groups, which allows for standardized treatment
Very high risk
25% recommendations based on prognosis. However, the NCCN recognizes that
80% heterogeneity exists within each risk group and multivariable models should
be used for risk stratification.
22%
70% High risk
Percent (%) of Patients
+ Nomograms are predictive instruments that combine prognostic variables and

provide individualized information beyond risk stratification.
60% 29%
Intermediate risk
+ Recurrent risk stratification differs from newly-diagnosed patients as a greater
50% 27% percentage of patients recur as high or very high-risk.
40% + Intermediate-risk patients can be differentiated as Favorable or Unfavorable.

23% Low risk
30% o ~ 85% of physicians stratify Intermediate Risk by Favorability (Table 4)b
21%
• 51% of newly-diagnosed patients are Favorable
20%
13%
Very low risk • 42% of recurrent patients are Favorable
10%
15%
10% + 83% and 71% of physicians make treatment decisions for newly diagnosed
0% locally advanced patients and Stage I-IV(M0) recurrent patients, respectively,
Newly Diagnosed Recurrent based on NCCN risk stratification (Table 5)c
Note: Refer to appendix for n values. a) QP1.4 / QP7A Of patients that you see with prostate cancer with newly diagnosed local/locally advanced disease / hormone sensitive
Stage IIV(M0) patients who experience a first recurrence, what percent are classified into each of the following risk groups based on NCCN? b) QP1.4A / QP7A.1 Of the newly-
diagnosed local/locally advanced / hormone sensitive Stage IIV(M0) patients who experience a first recurrence what percentage are classified as Favorable or Unfavorable CancerMPact® Treatment Architecture U.S., Prostate Cancer 27
intermediate risk based on NCCN? c) QP1.5 / QP7B Do you make treatment decisions for your prostate cancer patients with newly diagnosed Local/Locally Advanced disease
/ hormone sensitive Stage I-IV(M0) patients who experience a first recurrence based on NCCN risk stratification? Source: NCCN Guidelines v3.2023 Prostate Cancer
Role of biomarkers in prostate cancer
Several biomarkers are now used to guide systemic therapy treatment in prostate cancer: REPORTED FREQUENCY IN LITERATURE
HRR and BRCA: The PARP inhibitor olaparib was approved across all regions in 2020/21 for the treatment of
relapsed/refractory BRCA+ (HRR+ in the U.S.) mCRPC, with rucaparib also approved in the U.S for BRCA+
6%
Rate of inherited BRCA1/2 mutations in men with
mCRPC. PARP inhibitor combo therapies are also available in 1L mCRPC, with olaparib plus abiraterone
metastatic prostate cancer unselected for family
approved in the EU in late 2022, and the U.S. and Japan in 2023, with the latter two regions restricting the combo history2
to BRCA+ disease. Also in 2023, talazoparib plus enzalutamide was approved in the U.S. for HRR+ mCRPC
and single-dose niraparib plus abiraterone (Akeega®) was approved in the U.S. and EU for BRCA+ mCRPC.
In addition to informing treatment decisions, HRR positive results can inform genetic counseling for patients. 68%
Rate of PSMA+ disease as detected by PSMA-
PSMA: Prostate-specific membrane antigen (PSMA) has historically been used as a diagnostic marker of PET in biochemically recurrent patients3
metastatic disease and is now also an actionable biomarker. Based on results from the VISION trial, Pluvicto
(lutetium Lu 177 vipivotide tetraxetan) was approved in the U.S. and EU in 2022 for the treatment of PSMA-
positive mCRPC following progression on second-generation hormone therapy and a taxane. 19%-39%
Rate of AR-V7 positivity after progression on
AR-V7: An mRNA splice variant of the androgen receptor (AR) results in truncation of the ligand-binding domain, abiraterone or enzalutamide4
which is the target of second-generation hormone therapies abiraterone and enzalutamide. Patients with AR-V7
who progressed on these agents exhibit superior PFS and OS with taxane therapy.1 De novo AR-V7 is rare
and occurs in ~3% of patients but may be a marker of resistance to enzalutamide and abiraterone. 2%-5%
Rate of MMR deficiency in metastatic CRPC5,6
MSI-H / dMMR and TMB: NCCN guidelines recommend testing mCRPC patients for biomarkers tied to pan-
tumor drug approvals and suggest testing may be considered for mHSPC patients. MSI-H and dMMR guide pan-
tumor indications in the U.S., EU, Japan, and China for numerous agents, including pembrolizumab, 3%
dostarlimab, and several domestically-developed agents in China. In the U.S. and Japan, patients with TMB-H TMB-H rate in prostate cancer7
(tumor mutation burden high) disease are eligible for pembrolizumab following progression on prior therapy.
Based on NCCN Guidelines v3.2023 Prostate Cancer; 1. Scher, JAMA Oncol, 2016, 2. Pritchard, N Engl J Med, 2016, 3.
Pozdnyakov, Prost Canc and Prost Dis, 2023 4. Antonarakis, N Engl J Med, 2014, 5. Robinson, Cell, 2015, 6. Le, Science, 2017, 7. CancerMPact® Treatment Architecture U.S., Prostate Cancer 28
Yarchoan, JCI Insight, 2019
Stage IV: Biomarkers Jump to Table 6
Testing rates vary by biomarker, with around half of mHSPC patients tested for BRCA,
HRD/HRD/DDR, MSI/MMR and TMB, and one-third of patients tested for AR-V7
Biomarker Testing Rates, mHSPC, U.S., 2023 (Table 6)*
AR-V7 BRCA HRD / HRR / DDR MSI / MMR TMB
Prior to
Never Prior
1L, Never Prior to
Never Tested, Prior Never to 1L,
26% Tested, 1L, Never
Tested, 36% Prior to to 1L, Tested, 35%
1L, 44% 38% Tested,
63% 42% 49%
After 1L, 47% 53%
11% After After
After 1L, After 1L,
17% 1L, 1L,
12%
15% 14%
+ NCCN guidelines recommend AR-V7 testing to guide therapy selection for mCRPC, however, physicians indicate testing 37% of mHSPC patients are tested.
+ Though no biomarker-directed therapies are indicated for patients with mHSPC, NCCN guidelines recommend patients with metastatic disease undergo testing for
alterations in genes involved in DNA repair (BRCA1/2 and HRD/HRR/DRR), with testing occurring in approximately 50% of mHSPC patients.
+ Pembrolizumab is indicated for TMB-high or MSI-H/dMMR positive solid tumors and dostarlimab for dMMR positive solid tumors. Physicians report almost 50% of
patients are tested for these biomarkers.
Biomarker testing rates are similar in China and the U.S., and lower in the EU5. Japanese physicians rarely perform biomarker testing for these patients.
Literature-based positivity rates can be found on the Role of Biomarkers slide.
*QP1.1B (n=107): Of your hormone sensitive prostate cancer patients, what percent are tested for each biomarker at the following
points during the course of therapy?
Physicians use NGS testing in around one-third of HSPC patients
NGS Testing Patterns, HSPC

U.S., 2023 (Table 7)*
+ NCCN guidelines recommend germline and somatic genetic testing
for select prostate cancer patients based on family history, histology
and risk group. In the U.S., 36% of prostate patients are tested by
NGS prior to first-line treatment, with decreasing testing rates prior
Prior to 1L 36%
to subsequent lines of therapy.
NGS testing in HSPC patients prior to first-line therapy is

Time of Testing
highest the U.S. (36% ) and China (32%), with lower testing
in the EU5 (20%) and Japan (3%). Approximately one-third
Prior to 2L 31%
to one-quarter of U.S. patients are tested prior to second-
and third-line, while fewer are tested in the EU5 (~15%) and
Japan (~10%). In China, testing rates remain around one-
third of patients prior to each line of therapy.
Prior to 3L 25%
*QX1 (n=107): What percent of your hormone sensitive patients do you request tumor profiling or biomarker panel testing that use CancerMPact® Treatment Architecture U.S., Prostate Cancer 30
Next-Generation Sequencing (NGS) technology?
Over half of mCSPC patients are tested for BRCA, HRD/HRD/DDR, and MSI/MMR, while less
than half are tested for TMB, PSMA, MSI/MRR or AR-V7
Biomarker Testing Rates, mCRPC, U.S., 2023 (Table 8)*

AR-V7 BRCA HRD / HRR / DDR TMB MSI / MMR PSMA Expression
Never
Prior to Never Prior to Prior Never Prior to
Tested,
1L, Tested, 1L, Never to 1L, Tested, 1L,
Never 32% Never
30% Prior to 37% Tested, 39% 42% 43%
Tested, Prior to Tested, 50% 36%
1L, 47%
59% 1L, 46%
After 1L, 50%
After After
11% After 1L, After
After 1L, 1L, 1L,
18% 1L,
17% 14% 16%
15%
+ NCCN guidelines recommend AR-V7 testing for mCRPC patients to guide treatment following abiraterone and enzalutamide therapy.
+ NCCN guidelines recommend patients with metastatic prostate cancer undergo molecular testing for alterations genes involved in DNA repair. Several PARP inhibitors
are now approved in mCRPC, including olaparib for BRCAm patients in the 1L and R/R settings, talazoparib for HRRm 1L patients, and rucaparib for BRCAm R/R
patients. Physicians report 40% of patients are tested for HRD and BRCA mutations prior to first-line.
+ Around 45-50% of patients are tested for TMB-H and MSI/dMMR. Pembrolizumab is available for the treatment of TMB-H or MSI/dMMR positive relapsed disease
based on pan-tumor approvals. In 2021, dostarlimab also received pan-tumor for dMMR positive disease.
+ Lutetium Lu 177 vipivotide tetraxetan (Pluvicto) was approved in 2022 for PSMA positive mCRPC. Almost 40% of patients will be tested for PSMA expression.
Biomarker testing rates vary by region with highest testing rates in China followed closely by the U.S. EU5 physicians have lower overall testing rates except
for BRCA testing (~50%), while Japanese physicians test for BRCA mutations in around ~25% of mCRPC patients, but rarely for other biomarkers (5-10%).
Literature-based positivity rates can be found on the Role of Biomarkers slide.
*QP1.1.1B (n=106): Of your castration resistant prostate cancer patients, what percent are tested for each biomarker at the
following points during the course of therapy?
NGS testing rates are higher prior to first-line therapy for patients with CRPC
NGS Testing Patterns, CRPC

U.S., 2023 (Table 9)*
+ NCCN guidelines recommend germline and somatic genetic testing

Prior to 1L 47% for select prostate cancer patients based on family history, histology
and risk group. In the U.S., 47% of prostate patients are tested by
NGS prior to first-line treatment, with testing rates decreasing
through subsequent lines of therapy.
Time of Testing
Prior to 2L 28% NGS testing rates for patients with CRPC vary globally, with
testing rates prior to first-line highest in the U.S. (47%) and
China (37%) and lower in the EU5 (28%). In Japan, NGS
testing is uncommon, with only 3% of patients tested prior
to first-line and around 15% prior to second- and third-lines.
Prior to 3L 24%
*QX1 (n=106): What percent of your castration resistant patients do you request tumor profiling or biomarker panel testing that use CancerMPact® Treatment Architecture U.S., Prostate Cancer 32
Next-Generation Sequencing (NGS) technology?
Overview of
Treatment
Approaches
Treatment Overview Return to Table of Contents
Observation or active surveillance may be preferred for some patients with localized disease
Over-diagnosis and over-treatment of prostate cancer is a concern since prostate cancer can spread slowly and many older men with the disease
never require treatment. Active surveillance closely monitors disease and is preferred for patients with very-low-risk and low-risk disease who
have a life expectancy of ≥ 10 years and may also be considered for patients with favorable intermediate risk disease. Observation is preferred
for patients with very low-risk prostate cancer who have life expectancy < 10 years due to old age or other comorbidities. In the U.S., 33% of
patients with Stage I nmHSPC receive active surveillance prior to initial active therapy.
nmHSPC
STAGE I STAGE II STAGE III STAGE IV (M0) nmCRPC
Observation
Active Surveillance
Not commonly used Very commonly used
Note: Circle shadings are meant to qualitatively represent the strength of recommendation for use of each treatment modality within CancerMPact® Treatment Architecture U.S., Prostate Cancer 34
each stage, according to clinical guidelines, coupled with degree of utilization reported in physician survey.
Treatment Overview Jump to Table 10
Role of observation / no therapy in prostate cancer
Observation as Initial Management, Prostate Cancer, U.S., 2023 (Table 10)*
Percent of Patients Under Observation Who Eventually Receive Treatment‡ Duration (Months) of Observation Prior
to Active Therapy
Stage I 35% 31
Stage II 40% 21
HSPC
Stage III 44% 14

Stage IV(M0) 35% 13
CRPC
nmCRPC 41% 13
+ Observation may be best for elderly patients or patients with other comorbidities who are more likely to not die of prostate cancer. One study observed that only
13% of patients with local disease (T0-T2) developed metastases within 15 years after initial diagnosis, and only 11% of those patients died from prostate cancers.1
Thus, observation is preferred for patients with low-risk disease who have life expectancy of less than 10 years.1
+ Observation involves monitoring with a history and physical exam no more often than every 12 months until the onset of symptoms. Patients under observation
may begin palliative androgen deprivation therapy upon evidence of disease progression. Lower-risk patients tend to have longer duration of observation prior to
active therapy. Patients with Stage IV (M0) nmHSPC are slightly less likely to receive treatment compared to patients with Stage II-III HSPC or nmCRPC.
*QP3 / QP4 / QP22 / QP23 (see appendix for sample): What percent of your hormone sensitive Stage I-IV(M0) prostate cancer / recurrent non-
metastatic CRPC patients who receive “Observation/No therapy” as initial therapy eventually receive therapy? What is the average duration of
“Observation/No therapy” for your patients who eventually receive therapy? ‡ Note: Respondents answering 0% were recorded. 1. Johansson, JAMA,
1997; NCCN Guidelines Prostate v3.2023. 1. NCCN Guidelines v3.2023 Prostate Cancer.
Treatment Overview Jump to Table 10
Role of active surveillance in prostate cancer
Active Surveillance as Initial Management, Prostate Cancer, U.S., 2023 (Table 10)*
Duration (Months) of Active
Percent of Patients Under Active Surveillance Who Eventually Receive Treatment‡ Surveillance Prior to Active Therapy
Stage I 35% 32
Stage II 47% 26
HSPC
Stage III 58% 16

Stage IV(M0) 43% 17
13
CRPC
nmCRPC 49%
+ Active surveillance (formerly “expectant management”) involves actively monitoring the course of disease with the expectation to treat if the prostate cancer
progresses or if asymptomatic cancer becomes symptomatic. It is preferred for younger patients with indolent disease. Active surveillance requires PSA monitoring
no more often than every six months, and digital rectal examination (DRE), prostate biopsy, and multiparametric MRI (mpMRI) no more often than every 12 months. The
decision to initiate therapy depends on the onset of symptoms, which may lead to the initiation of curative therapy upon evidence of disease progression. While
managing a patient with active surveillance avoids the side effects of active therapy, a small proportion of patients may miss the opportunity for curative therapy and
experience pathologic fracture or urinary retention.
+ Patients with earlier stage disease tend to have a longer duration of active surveillance prior to active therapy.
*QP3 / QP4 / QP22 / QP23 (see appendix for sample): What percent of your hormone sensitive Stage I-IV(M0) prostate cancer /
recurrent non-metastatic CRPC patients who receive “Active Surveillance” as initial therapy eventually receive therapy? What is the
average duration of “Active Surveillance” for your patients who eventually receive therapy? ‡ Note: Respondents answering 0%
were recorded.
Early-stage lower-risk prostate cancer patients receive surgery and radiation-based therapies;
higher-risk patients receive systemic therapies, regardless of hormone sensitivity
Non-metastatic prostate cancer is managed with different treatment modalities depending on disease stage and castration sensitivity. Surgery
plays a greater role in Stage II-III nmHSPC disease. Radiation sees increasing usage through Stages I–III nmHSPC but is limited in Stage IV
nmHSPC and nmCRPC. Systemic therapy is more commonly used in later stage nmHSPC and nmCRPC.
nmHSPC
STAGE I STAGE II STAGE III STAGE IV (M0) nmCRPC
Surgery
Radiation
Systemic therapy
Systemic therapy-based treatments dominate the landscape for metastatic prostate cancer
regardless of symptomology or castration-sensitivity
Metastatic prostate cancer is managed predominantly with systemic therapy. Castration-sensitivity dictates the type of systemic therapy
administered, which can include androgen deprivation therapy, second generation anti-androgen therapy, chemotherapy, and immunotherapy.
Surgery and radiation are utilized in early-stage disease but have limited utility in metastatic disease.
mHSPC Asymptomatic mCRPC Symptomatic mCRPC
Surgery
Radiation
Systemic therapy
Treatment Overview Jump to nmHSPC, nmCRPC, mHSPC, mCRPC
Role of surgery in prostate cancer
Overall Surgery Use by Stage and

Hormone Sensitivity,
Surgery is common for patients with localized disease. Surgical options include radical prostatectomy, pelvic Prostate Cancer, U.S., 2023*
lymph node dissection, transurethral resection of the prostate, and cryosurgery. 100%
Radical prostatectomy is usually reserved for patients in good health who have a life expectancy of at least 10 90%
years and whose tumors are confined to the prostate gland. Following radical prostatectomy, PSA levels are 80%
monitored to identify patients at elevated risk of disease recurrence. Complications of radical prostatectomy can

include blood loss, urinary incontinence, urethral stricture, impotence, and morbidity associated with general 70%
anesthesia and a major surgical procedure. 60%
Pelvic lymph node dissection (PLND) may be performed in addition to radical prostatectomy for patients with 50%
intermediate- and high-risk localized disease and other select patients. Lymphadenectomy may be performed
40%
laparoscopically, as an open procedure, or robotically.
30%
Transurethral resection of the prostate (TURP) is used to remove the part of the prostate gland that surrounds
20% 40% 42%
the urethra in patients who are unable to have a radical prostatectomy due to advanced age or serious medical 31%
conditions. TURP can be used to relieve symptoms prior to systemic or radiotherapy but is not expected to cure 10% 16% 15% 14% 14%
the disease or definitively remove the tumor. 12%
0%
Cryosurgery (cryotherapy or cryoablation) is a minimally invasive procedure that involves destruction of prostate
cancer cells by intermittent local freezing of prostate tissue. Cryosurgery is not recommended as routine
primary therapy due to a lack of long-term data and is only recommended in the absence of metastatic disease.
Cryosurgery is associated with urinary retention, incontinence, impotence, and rectourethral fistula.
nmHSPC
*QP2 / QP21 / QP30 / QP40 (see appendix for sample): Of patients that you see with Stage I-IV(M0) prostate cancer / non-
metastatic CRPC disease / hormone sensitive Stage IV (M1) prostate cancer / metastatic CRPC disease, approximately what CancerMPact® Treatment Architecture U.S., Prostate Cancer 39
percent of patients are treated with each of the modalities listed below for initial therapy?
Role of radiotherapy in prostate cancer
Overall Radiotherapy Use by

Stage and Hormone Sensitivity,
Prostate Cancer, U.S., 2023*
Radiotherapy (RT) for the treatment of prostate cancer includes external beam radiotherapy (EBRT),
proton radiation, and brachytherapy. Performance status, risk stratification and toxicity should be 100%
taken into consideration for choosing which specific RT modality is appropriate for the patient. Radiation 90%
usually eliminates the need for surgery, and patients considered poor medical candidates for radical
80%
prostatectomy might be treated with acceptably low complications if care is given to the delivery

technique. EBRT is the most commonly used form of RT. For patients with organ-confined disease, 70%
EBRT has been shown to be as effective as radical prostatectomy.1 RT can also be delivered after
60%
extra-peritoneal lymph node dissection.
50%
RT efficacy and its effect on long-term patient outcome is largely dependent on disease stage. Patients
40%
who do not achieve a good response to RT may still undergo salvage prostatectomy. For patients with
advanced disease, RT may be used to palliatively to reduce tumor size and provide symptomatic relief. 30% 60%
44%
20%
33%
26%
10% 21% 19% 21%
17%
0%
nmHSPC
metastatic CRPC disease / hormone sensitive Stage IV (M1) prostate cancer / metastatic CRPC disease, approximately CancerMPact® Treatment Architecture U.S., Prostate Cancer 40
what percent of patients are treated with each of the modalities listed below for initial therapy? 1. Wolff, Eur J Cancer, 2015
Role of systemic therapy in prostate cancer
Overall Systemic Therapy Use by

Stage and Hormone Sensitivity,
Androgen deprivation therapy (ADT) is the backbone of PARP inhibitors first entered the global prostate treatment Prostate Cancer, U.S., 2023*
systemic therapy for the treatment of advanced prostate space in second-line mCRPC, with olaparib first approved 100%
cancer and can be used as neoadjuvant / adjuvant therapy in the U.S. for HRR+ mCRPC and rucaparib approved in
with or without RT for localized disease. ADTs are analogs the U.S. for the treatment of BRCA+ mCRPC. Olaparib has 90%
of luteinizing hormone-releasing hormone (LHRH) or since been similarly approved across all global regions.
80%
gonadotropin-releasing hormone (GnRH) receptor

inhibitors. ADTs are equally effective in decreasing serum PARP inhibitors are now also approved in combination with 70%
testosterone levels as surgical castration (orchiectomy).1 second-generation anti-androgen therapies for first-line
First-generation anti-androgen therapies target the treatment of mCRPC. In late 2022, olaparib + abiraterone 60%
androgen receptor (AR) and include bicalutamide, was first approved in the EU5 for mCRPC independent of
50%
flutamide, and nilutamide. Combining an ADT with a first- BRCA status. In mid-2023, the same combination was
90% 87% 88%
generation anti-androgen therapy is more effective than approved in the U.S., though the indication was restricted to 40% 81% 79%
using an ADT alone. BRCA+ patients. In mid-2023, talazoparib + enzalutamide
was approved in the U.S. for HRD+ mCRPC, and a 30%
Second-generation anti-androgen therapies include coformulation of niraparib + abiraterone was approved in 50%
20%
abiraterone, enzalutamide, apalutamide, darolutamide, and the U.S. and EU5 for BRCA+ mCRPC patients.
rezvilutamide (China only) and are available for patients 10% 24%
resistant to traditional ADT. Sipuleucel-T is an autologous vaccine approved in the U.S. 13%
and EU5 for treatment of asymptomatic and mildly 0%
Other systemic therapies include chemotherapy. symptomatic CRPC. Radium-223 dichloride is an alpha-
Docetaxel in combination with ADT has been shown to emitting radiopharmaceutical approved in all regions for
improve overall survival for patients with high-risk localized mCRPC. Lutetium Lu 177 vipivotide tetraxetan is a
and metastatic disease.2-3 Cabazitaxel was originally PSMA-targeted radiopharmaceutical approved in the U.S.
approved for CRPC patients who failed docetaxel-based and EU5 for PSMA-positive mCRPC patients who have
treatment but has since demonstrated a benefit in progressed on an androgen-receptor inhibitor and
chemotherapy-naïve mCRPC patients.4-5 docetaxel. nmHSPC
metastatic CRPC disease / hormone sensitive Stage IV (M1) prostate cancer / metastatic CRPC disease, approximately what
percent of patients are treated with each of the modalities listed below for initial therapy? 1. Trachtenberg, J Urol, 2002, 2.
Sweeney, N Eng J Med, 2015, 3. James, Lancet, 2016, 4. de Bono, Lancet, 2010, 5. Oudard, J Clin Oncol, 2017.
U.S. regulatory approval timeline in prostate cancer
Jemperli*, 2L,
Xtandi, dMMR
nmCRPC
For approvals occurring in Pluvicto,

2012 and earlier, see PSMA+, prior ARI and
Regulatory Approval Details Nubeqa, Lynparza, 2L
nmCRPC taxane mCRPC
for Branded Agents HRR+, mCRPC
Erleada, Lynparza + abiraterone,
nmCRPC Keytruda*, 2L, BRCAm, mCRPC
TMB-H
Xofigo,
Symptomatic mCRPC
≤ 2012 2013 2014 2015 2016 2017 2018 2019 2020 2021 2022 2023
Orgovyx, Akeega,
Xtandi, advanced prostate BRCAm, mCRPC
Chemo-naïve mCRPC cancer
Rubraca, 2L Talzenna + Xtandi,

Yonsa, BRCA+ mCRPC HRRm, mCRPC
mCRPC Nubeqa + docetaxel
Xtandi,
mHSPC
Zytiga, newly-diagnosed mHSPC
high-risk mHSPC
Keytruda*, 2L, Erleada,

MSI-H/dMMR mHSPC
Notes: Please refer to Appendix (Table A.1) for definitions of abbreviations; Dates displayed indicate date of initial approval. CancerMPact® Treatment Architecture U.S., Prostate Cancer 42
*Pan-tumor approval.
Regulatory approval details for branded agents in prostate cancer (i)

In combination U.S. FDA EU JP MHLW CN NMPA
Agent* Manufacturer(s) MOA Indication* Biomarker
with… Approval Approval Approval Approval
Akeega® PARP inhibitor

prednisone / Apr-23 (EMA)
(niraparib and Janssen (U.S., EU) and androgen mCRPC BRCAm Aug-23 None None
prednisolone Jul-23 (MHRA)
abiraterone) antagonist
AiRuiEn Androgen High-volume Jun-22

Hengrui (CN) ADT None None None None
(rezvilutamide) antagonist mHSPC (cond)
Advanced solid
tumors following
BaiZeAn MSI-H / Mar-22
BeiGene (CN) Anti-PD-1 mAb progression and with None None None None
(tislelizumab) no satisfactory
dMMR (cond)
alternatives
Advanced solid
Alphamab, 3D tumors following
EnWeiDa MSI-H / Nov-21
Medicines, and Simcere Anti-PD-L1 mAb progression and with None None None None
(envafolimab) no satisfactory
dMMR (cond)
(CN)
alternatives
Janssen (U.S., EU, nmCRPC ADT Feb-18 Jan-19 Mar-19 Sep-19

Erleada® Androgen
CN) None
(apalutamide) antagonist
Nippon Shinyaku (JP) mHSPC ADT Sep-19 Jan-20 May-20 Aug-20
Note: Please refer to Appendix (Table A.1) for definitions of abbreviations. *These approvals are current as of the date of
publication of this report and stated line of therapy is an approximation if not explicitly stated in the regulatory label; please refer to CancerMPact® Treatment Architecture U.S., Prostate Cancer 43
official product labels for most current approval status and nuanced description of the approved indications by market.
Regulatory approval details for branded agents in prostate cancer (ii)

Advanced,
hormone- None None Dec-08 Feb-09 Jun-12 Sep-18
dependent
High-risk localized
Ferring and locally
Firmagon® (U.S., Oct-21 (EMA)
Pharmaceuticals advanced RT None None None None
EU, CN) GnRH receptor Oct-22 (MHRA)
(U.S., EU) hormone-
Gonax® (JP) antagonist
dependent
Astellas (JP)
(degarelix)
Pfizer (CN) Neoadjuvant prior
to RT, high-risk
Oct-21 (EMA)
advanced None None None Oct-22 (MHRA)
None None
hormone
dependent
Advanced solid
tumors following
HanSiZhuang Mar-22
Henlius (CN) Anti-PD-1 mAb progression and None MSI-H None None None
(serplulimab) with no satisfactory
(cond)
alternatives
Advanced solid Aug-21

tumors, following
Jemperli® (accel)
GSK (U.S., EU) Anti-PD-1 mAb progression with None dMMR None None None
(dostarlimab) no satisfactory
Feb-23
alternatives (full)
Jevtana® Microtubule Docetaxel pre-

Sanofi (U.S., EU, JP) prednisone None Jun-10 Mar-11 Jul-14 None
(cabazitaxel) inhibitor treated mCRPC
Regulatory approval details for branded agents in prostate cancer (iii)

Advanced solid May-17
tumors, following
MSI-H / (accel)
progression with None None Dec-18 Sep-23
no satisfactory
dMMR Mar-2023
alternatives (full)
Keytruda® Merck & Co (U.S.)
Anti-PD-1 mAb
(pembrolizumab) MSD (EU, JP, CN) Advanced solid
tumors, following TMB-H
Jun-20
progression with None (≥10 mt per None Feb-22 None
(accel)
no satisfactory megabase)
alternatives
Lupron Depot
(U.S., EU);
Abbvie (U.S., EU)
Leuplin SR (JP); GnRH agonist Advanced None None 1985 1989 Oct-92 Jul-02
Takeda (JP, CN)
Enantone (CN)
(leuprolide)
mCRPC
HRRm May-20 None None None
pre-treated with None
AstraZeneca / Merck second-gen ARI Jun-21
Lynparza® & Co (U.S.) BRCAm None Nov-20 Dec-20
PARP inhibitor (cond)
(olaparib) AstraZeneca / MSD
(EU, JP, CN) Dec-22 (EMA)
abiraterone + None None None None
Mar-23 (MHRA)
mCRPC (prednisone /
prednisolone)
BRCAm May-23 None Aug-23 None
Regulatory approval details for branded agents in prostate cancer (iv)

Feb-21
nmCRPC ADT None Jul-19 Mar-20 Jan-20
(cond)
Nubeqa® Bayer Androgen
(darolutamide) (U.S., EU, JP, CN) antagonist
Nov-22(MHRA)
mHSPC ADT, docetaxel None Aug-22 Mar-23 (EMA)
Feb-23 Mar-23
Myovant / Pfizer (U.S.)

Orgovyx GnRH receptor Apr-22 (EMA)
Accord Healthcare mHSPC None None Dec-20 None None
(relugolix) antagonist Jun-22 (MHRA)
(EU/UK)
Pluvicto®
mCRPC
(lutetium Lu 177 Novartis PSMA-targeted Dec-22 (EMA)
pretreated with None PSMA Mar-22 None None
vipivotide (U.S., EU) radioligand
ARI and taxane
Aug-22(MHRA)
tetraxetan)
Advanced solid
tumors, following
progression on at
PuYouHeng MSI-H / Jul-22
Lepu Biopharma (CN) Anti-PD-1 mAb least one previous None None None None
(pucotenlimab) line of therapy,
dMMR (cond)
with no satisfactory
alternatives
Regulatory approval details for branded agents in prostate cancer (v)

Asymptomatic or
Autologous
Provenge® minimally
Dendreon (U.S., EU) cellular None None Apr-10 Sep-13 None None
(sipuleucel-T) immunotherapy
symptomatic
mCRPC
Androgen
Rubraca® Pharma & Schweiz receptor- and May-20
PARP inhibitor None BRCAm None None None
(rucaparib) GmbH (U.S., EU) taxane-pre-treated (accel)
mCRPC
Talzenna®
Pfizer PARP inhibitor mCRPC enzalutamide HRRm Jun-23 None None None
(talazoparib)
Trelstar® (U.S.)
Verity
Decapeptyl®(EU)
Pharmaceuticals
Diphereline® (CN) GnRH agonist Advanced None None Jun-00 Off patent1 None Dec-08
(U.S.)
(triptorelin
Ipsen (EU, CN)
pamoate)
Symptomatic
alpha-particle
Xofigo® mCRPC with bone
Bayer (U.S., EU, JP, emitting
(radium-223 metastases and None None May-13 Nov-13 Mar-16 Aug-20
CN) radioactive
no known visceral
dichloride) agent
metastatic disease
publication of this report and stated line of therapy is an approximation if not explicitly stated in the regulatory label; please refer to
official product labels for most current approval status and nuanced description of the approved indications by market. CancerMPact® Treatment Architecture U.S., Prostate Cancer 47
1. No generics are currently available for Decapeptyl.
Regulatory approval details for branded agents in prostate cancer (vi)

Docetaxel-
Aug-12 Jun-13 None None
pretreated mCRPC
Chemotherapy
Astellas (U.S., EU, JP, Sep-14 Dec-14 None Nov-19
Xtandi® Androgen naïve mCRPC ADT None
CN)
(enzalutamide) antagonist
Pfizer (U.S.) CRPC None None Mar-14 None
nmCRPC Jul-18 Oct-18 None Nov-20
mHSPC Dec-19 May-21 Jun-20 None

mCRPC talazoparib HRRm Jun-23 None None None
Yonsa
(abiraterone
Sun Pharmaceutical CYP17 ADT, methyl-
acetate; mCRPC None May-18 None None None
Industries (U.S.) inhibitor prednisolone
micronized
formulation)1
1991 1996
Zoladex® 3.6 mg 3.6 mg
(Zoladex) (Zoladex)
Zoladex LA® TerSera Therapeutics
LHRH analog Advanced None None 1996 1995
(goserelin LLC./ AstraZeneca Jan-02 Dec-11
acetate) 10.8 mg 10.8 mg
(Zoladex LA) (Zoladex LA)
official product labels for most current approval status and nuanced description of the appr, oved indications by market. 1. Yonsa is CancerMPact® Treatment Architecture U.S., Prostate Cancer 48
a novel formulation of abiraterone and is not available as a generic in the U.S.
Regulatory approval details for branded agents in prostate cancer (vii)

Docetaxel pre-
Apr-11 Sep-11 None None
treated mCRPC
Chemotherapy- ADT Dec-12 Jan-13 None None
naïve mCRPC (prednisone / None
mCRPC prednisolone) None None Jul-14 May-15
Newly-diagnosed
Feb-18 Nov-17 Feb-18 Nov-18
high-risk mHSPC
Zytiga® Janssen (U.S., EU,
CYP17 olaparib,
(abiraterone JP, CN), Dec-22 (EMA)
inhibitor mCRPC (prednisone / None None None None
acetate)1 Nippon Shinyaku (JP) Mar-23 (MHRA)
prednisolone)
olaparib
mCRPC (prednisone / BRCAm May-23 None Aug-23 None
prednisolone)
niraparib
Apr-23 (EMA)
mCRPC (prednisone / BRCAm Aug-23 Jul-23 (MHRA)
None None
prednisolone)
official product labels for most current approval status and nuanced description of the appr, oved indications by market. 1. Generic CancerMPact® Treatment Architecture U.S., Prostate Cancer 49
abiraterone is available in the U.S., EU5 and CN
Dosing and administration for common agents / regimens in prostate cancer (i)
Agent / Regimen Mechanism of Action Formulation Dose / Administration*
Combination Regimens
abiraterone + prednisone
abiraterone CYP17 inhibitor PO 1,000 mg BID (mCRPC) or 1000 mg QD (mHSPC), d1-28, repeat cycle q4w
prednisone corticosteroid PO 5 mg BID (mCRPC) or 5 mg QD (mHSPC) d1-28, repeat cycle q4w
abiraterone + methylprednisolone
abiraterone CYP17 inhibitor PO 500 mg QD
methylprednisolone Corticosteroid PO 4 mg BID
bicalutamide + degarelix
bicalutamide androgen antagonist PO 80 mg QD
degarelix GnRH receptor antagonist SC 240 mg initial dose, day 1, followed by maintenance 80 mg, day 1, repeat cycle q4w
bicalutamide + leuprolide
bicalutamide androgen antagonist PO 50 mg QD (80mg QD in Japan)
leuprolide GnRH agonist IM Depot 22.5 mg q12w
bicalutamide + goserelin
bicalutamide androgen antagonist PO 50 mg QD
goserelin GnRH agonist SC Implant 3.6 mg q4w
Notes: Please refer to Appendix (Table A.1) for definitions of abbreviations. *Dosing / admin according to approved regulatory label,
unless as noted. Dosed until progression or unacceptable tolerability unless a fixed number of cycles is noted. Agent / Regimen CancerMPact® Treatment Architecture U.S., Prostate Cancer 50
listed may not be approved in all regions.
Dosing and administration for common agents / regimens in prostate cancer (ii)
Combination Regimens
cabazitaxel + prednisone
cabazitaxel microtubule inhibitor IV 25 mg/m2 over 1 hour, day 1, repeat cycle q3w
prednisone corticosteroid PO 10 mg BID, d1-21, repeat cycle q3w
docetaxel + prednisone
docetaxel microtubule inhibitor IV 75 mg/m2 over 1 hour, day 1, repeat cycle q3w for 6 cycles
prednisone corticosteroid PO 5 mg BID, d1-21, repeat cycle q3w for 6 cycles
flutamide + leuprolide
flutamide androgen antagonist PO 250 mg TID (125 mg in Japan)
leuprolide GnRH agonist IM Depot 22.5 mg q12w
flutamide + goserelin
flutamide androgen antagonist PO 250 mg TID (125 mg in Japan)
goserelin GnRH agonist SC Implant 3.6 mg q4w
olaparib + abiraterone
olaparib PARP inhibitor PO 300 mg BID
abiraterone androgen antagonist PO 1000 mg BID
talazoparib + enzalutamide
talazoparib PARP inhibitor PO 0.5 mg QD
enzalutamide androgen antagonist PO 160 mg QD
Dosing and administration for common agents / regimens in prostate cancer (iii)
Single-Agent Regimens
apalutamide androgen antagonist PO 240 mg QD, d1-28, repeat cycle q4w
bicalutamide androgen antagonist PO 50 mg QD (80 mg in Japan), d1-28, repeat cycle q4w
darolutamide androgen antagonist PO 600 mg BID, d1-28, repeat cycle q4w
degarelix GnRH receptor antagonist SC 240 mg initial dose, day 1, followed by maintenance 80 mg, day 1, repeat cycle q4w
500 mg, day 1; q3w (dose 1-4)

dostarlimab anti-PD-1 mAb IV
1000 mg, day 1; q6w (dose 5 onwards)
envafolimab Anti-PD-L1 mAb SC 150 mg, qw, until disease progression or unacceptable toxicity
enzalutamide androgen antagonist PO 160 mg QD, d1-28, repeat cycle q4w
flutamide androgen antagonist PO 250 mg TID, d1-28, repeat cycle q4w
goserelin GnRH agonist SC/IM Implant 3.6 mg q4w (SC) or implant 10.8 mg q12w (IM)
Depot 7.5 mg injection q4w OR 22.5 mg injection q12w OR 30 mg injection q16w OR 46 mg

leuprolide GnRH agonist IM
q24w
lutetium Lu 177
PSMA radioligand IV 7.4 GBq (200 mCi) Q6W for up to 6 doses, or until progression or unacceptable toxicity
vipivotide tetraxetan
Dosing and administration for common agents / regimens in prostate cancer (iv)
Single-Agent Regimens
niraparib/abiraterone PARP inhibitor + androgen
PO 200 mg/500mg niraparib/abiraterone acetate QD
acetate antagonist
olaparib PARP inhibitor IV 300 mg BID until disease progression or unacceptable toxicity
200 mg, day 1; q3w

pembrolizumab anti-PD-1 mAb IV 400 mg, day 1; q6w
2 mg/kg (up to 200 mg); q3w (pediatrics)
pucotenlimab Anti-PD-1 mAb IV 200 mg, q3w, until disease progression or unacceptable toxicity
alpha-particle emitting radioactive

radium-223 dichloride Injection 55 kBq (1.49 microcurie)/kg body weight q4w for 6 injections
agent
relugolix GnRH receptor antagonist PO 360 mg initial dose, followed by 120 mg QD, until progression
rezvilutamide Androgen antagonist PO 240 mg QD
rucaparib PARP inhibitor PO 600 mg BID until disease progression or unacceptable toxicity
serplulimab Anti-PD-1 mAb IV 3 mg/kg, q2w, until disease progression or unacceptable toxicity
3 doses given over 1 hour at 2-week intervals; each dose includes a minimum of 50 million
sipuleucel-T autologous cellular immunotherapy IV
autologous CD54+ cells activated with PAP-GM-CSF
tislelizumab Anti-PD-1 mAb IV 200 mg, q3w, until disease progression or unacceptable toxicity
triptorelin GnRH agonist IM 3.75 mg, q4w OR 11.25 mg, q12w, or 22.5mg, q24w
Treatment:
Non-Metastatic
Hormone Sensitive
Prostate Cancer
(nmHSPC)
nmHSPC: Treatment Jump to Table 11
Non-metastatic hormone sensitive prostate cancer (nmHSPC) is managed using different

modalities depending on stage
Initial Treatment Modality by Stage,

nmHSPC, U.S., 2023 (Table 11)* + Clinical guidelines recommend treatment approaches for patients with
localized disease based on life expectancy and risk stratification. Active
100%
Other surveillance and observation are recommended for lower-risk patients, while
10% 7% RT and systemic therapy are preferred for higher risk disease.
90% 5% 5% Surgery, RT
8%
80%
+ For Stage I disease, around 40% of patients undergo observation or active
9% 13% Surgery, RT, systemic surveillance, which decreases in later stage. Systemic therapy is increasingly
9%
therapy common for patients with more advanced disease.
70% 7%
18% Systemic therapy only

51%
60%
Surgery, systemic therapy Treatment approaches have been consistent over the last few years
24%
50% 27% in the U.S.
RT, systemic therapy
40% 33%
13% Observation / No therapy Surgery alone is common for early-stage disease across all regions.
30% Active surveillance for Stage I patients is highest in the U.S. (33%),
15%
19% RT ONLY comparable in Japan (26%) and EU5 (23%), but uncommon in China
20% (9%). Systemic therapy alone becomes more prevalent in later stage
30% Active Surveillance disease and is preferred for Stage IV (M0) patients in Japan (65%),
10% 24% the U.S. (51%), and EU5 (37%), though systemic therapy alone is
18% 6%
Surgery ONLY lower in CN (21%).
0%
Stage I Stage II Stage III Stage IV
(M0)
*QP2 (n=91 Stage I, n=98 Stage II, n=102 Stage III, n=103 Stage IV (M0)): Of patients that you see with Stage I-IV(M0) prostate
cancer, approximately what percent of patients are treated with each of the modalities listed below for initial therapy?
Intensity modulated radiotherapy (IMRT) is the preferred RT across all stages of nmHSPC
Type of Radiotherapy, nmHSPC,

U.S., 2023 (Table 12)*
100% + External beam radiotherapy (EBRT) is a common radiotherapy technique
13% 11% 9% 12% used in prostate cancer. EBRT is as effective as radical prostatectomy in
90% patients with organ-confined disease but may result in acute cystitis, proctitis,
Any other type of EBRT
5% 8% 12% and sometimes enteritis, but is associated with increased pelvic damage
11%
80% compared to other forms of radiotherapy.
19% 19% 17%
70% + Three-dimensional (3D) intensity modulated radiotherapy (IMRT) is
23% favored over traditional 3D conformal radiation therapy (3D-CRT) since it

Proton beam radiation
60%
therapy reduces the risk of gastrointestinal toxicities and rates of salvage therapy.
50% o IMRT has become the preferred form of radiotherapy with 55-65%
utilization across all stages of nmHSPC.
40%
SBRT + Stereotactic body radiotherapy (SBRT) and proton beam radiation therapy
30% 63% 62% 62% (PBRT) are also sometimes used.
54%
20%
IMRT has remained the most common RT approach for several years.
IMRT
10%
IMRT is preferred across all stages in the U.S., EU5, and Japan (all
0% 55-65%). In China, IMRT and SBRT are equally used across all
Stage I Stage II Stage III Stage IV stages (25-35%).
(M0)
*QP6 (n=71 Stage I, n=90 Stage II, n=92 Stage III, n=69 Stage IV (M0)): Of your hormone sensitive Stage I-IV(M0) prostate cancer
patients who receive “Radiotherapy (RT) (including external beam radiotherapy (EBRT))”, what percent receive proton beam CancerMPact® Treatment Architecture U.S., Prostate Cancer 56
radiation therapy, stereotactic body radiation therapy (SBRT), intensity-modulated radiotherapy (IMRT), or another type of EBRT?
nmHSPC: Treatment Return to Table of Contents
Clinical trial data that supported approvals in nmHSPC (i)

Trial EORTC [No Trial Identifier] RTOG 85-31
RT, neoadjuvant,
Trial arms RT, goserelin RT concurrent and adjuvant RT RT, adjuvant goserelin RT
ADT
Sample size 195 196 102 104 477 468
Geography EU, ROW U.S. U.S.
Biomarker None None None
Indication Stage T1-T2 WHO Grade 3 OR T3-T4 N0-1 M0 Stage T1b-T2b, NX, M0 Stage T3 or Stage T1 and T2 with nodal involvement
10-yr local failure rate: 10-yr local failure rate:

5-yr DFS: 74% 5-yr DFS: 40% 5-yr DFS: 82% 5-yr DFS: 57%
Disease Free Survival 23% 38%
HR: 0.34, p<0.0001 HR: 2.30, p=0.002 p<0.0001
5-yr OS: 78% 5-yr OS: 62% 5-yr OS: 88% 5-yr OS: 78% 10-yr OS: 49% 10-yr OS: 39%
Overall Survival
HR: 0.51, p<0.0001 HR: 2.07, p=0.04 p=0.002
Total Grade 3/4 AEs Not reported Not reported Not reported Not reported Not reported Not reported
AE-related
Not reported Not reported Not reported Not reported Not reported Not reported
discontinuation rate
Impotence (26%), Impotence (21%),

Most common Grade
Not reported Not reported Rectal bleeding (3%), Rectal bleeding (2%), Not reported Not reported
3/4 AEs*
Hematuria (3%) Hematuria (3%)
Citation Bolla, Lancet, 2002 D'Amico, JAMA, 2004 Pilepich, Int J Radiat Oncol Biol Phys, 2005
Notes: The primary endpoint(s) for each trial are denoted by using bold font. Older studies may not possess a trial identifier code or
have a stipulated primary endpoint per-protocol. Please refer to Appendix (Table A.1) for definitions of abbreviations. CancerMPact® Treatment Architecture U.S., Prostate Cancer 57
*Shown are the top 3 Grade 3/4 adverse events reported for the experimental arm or arm with the highest efficacy.
Clinical trial data that supported approvals in nmHSPC (ii)

GETUG 12
Trial RTOG 99-02 RTOG 86-10
NCT00055731
Neoadjuvant and
24-mo goserelin and 4-mo goserelin and docetaxel, estramustine,
Trial arms concurrent goserelin and RT ADT only
flutamide, RT flutamide, RT ADT
flutamide, RT
Sample size 758 763 224 232 207 206
Geography U.S. U.S. EU
Patient Segment None None None
Treatment Naive, T3–T4N0-XM0, Gleason score of ≥8,
Indication Stage T2c-T4N0-X, PSA <150 ng/mL N0-N1 M0
or PSA >20 ng/mL
12-yr RFS: 49.4% 12-yr RFS: 36.3%
10-yr DFS: 22.5% 10-yr DFS: 13.2% 10-yr DFS: 11.2% 10-yr DFS: 3.4%
Disease Free Survival mRFS: 11.6 mos mRFS: 8.1 mos
p<0.0001 p<0.0001 HR: 0.71, p=0.0109
10-yr OS: 42.6% 10-yr OS: 33.8% 12-yr PC-specific OS: 12-yr PC-specific OS:
10-yr OS: 53.9% 10-yr OS: 51.6%
Overall Survival mOS: 8.7 mos mOS: 7.3 mos 88.2% 83.9%
p=0.36 p=0.12 HR: 0.70, p=0.0109
Total Grade 3/4 AEs Not reported Not reported Late toxicities: 9% Late toxicities: 11% ≥Grade 2: 21% ≥Grade 2: 18%
AE-related
Acute RT toxicity (8%) Acute RT toxicity (10%) Grade 3 EBRT toxicity Grade 3 EBRT toxicity
Bladder (3%) Bladder (5%) Long term Long term
(4%), (4%),
Most common Grade Late RT toxicity (10%) Late RT toxicity (7%) Genitourinary (2%), Genitourinary (2%),
Acute Grade 3 (2%), Acute Grade 3 (4%),
3/4 AEs* Bladder (5%) Bladder (4%) Bowel-colon (1%), Bowel-colon (0%),
Hormone toxicity (5%) Hormone toxicity (5%) Fatal cardiac events Fatal cardiac events
Rectum-anus (1%) Rectum-anus (3%)
Elevated AST (2%) Elevated AST (1%) (12.5%) (9.1%)
Citation Horwitz, J Clin Oncol, 2008 Roach, J Clin Oncol, 2008 Fizazi, Lancet Oncol, 2015; Fizazi, Ann Oncol, 2018
Clinical trial data that supported approvals in nmHSPC (iii)

RTOG 99-10
Trial RTOG 99-02
NCT00005044
ADT, RT, 4 cycles of
Trial arms 28-week ADT  RT, ADT 8-week ADT  RT, ADT paclitaxel, estramustine ADT, RT
and etoposide
Sample size 737 752 200 197
Geography U.S., ROW U.S., ROW
Patient Segment None None
T1b-T4, Gleason score 2-6 and PSA >10-100 ng/mL, or T1b-T4

PSA 20-100 ng/mL and Gleason score ≥7 or Stage ≥T2
Indication Gleason score 7 PSA<20 ng/mL, or T1b-1c Gleason score 8-10
and Gleason score ≥8 N0M0
and PSA<10 ng/mL, N0M0
10-yr DSS: 96% 10-yr DSS: 95% 10-yr DFS: 26% 10-yr DFS: 22%
Disease Free Survival
HR: 0.81, p=0.45 HR: 0.94, p=0.61
10-yr OS: 67% 10-yr OS: 66% 10-yr OS: 63% 10-yr OS: 65%
Overall Survival
HR: 0.95, p=0.62 HR: 1.04, p=0.81
Total Grade 3/4 AEs Early: 26%, Late: 8% Early: 16%, Late: 10% 73.0% 40.4%
AE-related
Not reported Not reported Not reported Not reported
Early Early
Most common Grade Sexual (17%), Sexual (8%),
Not reported Not reported
3/4 AEs* Urinary (5%), Urinary (4%),
G: (3%) GI (2%)
Citation Pisansky, J Clin Oncol, 2015 Rosenthal, Int J Radiat Oncol Biol Phys, 2015
Clinical trial data that supported approvals in nmHSPC (iv)

STAMPEDE DC-990-0056
Trial
(NCT00268476, ISRCTN78818544) NCT00223171
Trial arms abiraterone, prednisone, ADT ADT Only 36-month ADT, RT 18-month ADT, RT
Sample size 960 M0 + M1 957 M0 + M1 310 320

Geography EU ROW
Biomarker None None
Indication Newly diagnosed metastatic node positive or high-risk locally advanced High-risk prostate cancer Stage T3-T4 or PSA>20ng/mL or Gleason score >7
5-yr FFS: 45% 5-yr FFS: 13%

10-yr DFS: 45% 10-yr DFS: 39%
Disease Free Survival mean FFS: 43.9 mos mean FFS: 30.0 mos
HR: 0.29, p<0.001; M0 - FFS improvement over ADT: 79%, HR: 0.21 HR: 0.84, p=0.08
5-yr OS: 60% 5-yr OS: 41% 10-yr OS: 62% 10-yr OS: 62%
Overall Survival
HR: 0.63, p<0.001; M0 - OS improvement over ADT, 25% HR: 0.75 HR: 1.02, p=0.8
Total Grade 3/4 AEs 47% 33% Not reported Not reported
AE-related
Endocrine disorder (14%), Endocrine disorder (14%), Acute toxicity Acute toxicity
Most common Grade
Cardiovascular disorders (10%), Cardiovascular disorders (4%), GI toxicity (2.0%), GI toxicity (0.6%),
3/4 AEs*
Musculoskeletal disorders (7%) Musculoskeletal disorders (5%) GU toxicity (1.0%) GU toxicity (2.6%)
Citation James, N Engl J Med, 2017; James, Int J Cancer, 2022 Nabid, Eur Urol, 2018
Clinical trial data that supported approvals in nmHSPC (v)

HERO
Trial
NCT03085095
Trial arms relugolix leuprolide
Sample size 622 308
Geography U.S., EU, JP, ROW
Patient Segment Stage III-IV androgen-sensitive
96.7% 88.8%
Sustained Castration
Rate
95% CI: 94.9 to 97.9, P<0.001
79.4% 19.8%
PSA response
(day 15)
P<0.001
Total Grade 3/4 AEs 18% 20.5%
AE-related
Hypertension (1.6%) Hypertension (0.6%)

Most common Grade Hot flash (0.6%) Hot flash (0%)
3/4 AEs* Fatigue (0.3%) Fatigue (0%)
Arthralgia (0.3%) Arthralgia (0%)
Citation Shore, N Eng J Med, 2020
nmHSPC: Treatment Jump to Table 13 and Table 53
For newly diagnosed nmHSPC, leuprolide with or without an anti-androgen agent dominates
the treatment landscape
Systemic Therapy Utilization, Newly-Diagnosed
nmHSPC, U.S., 2023 (Table 13)a
100% + The LHRH agonist leuprolide has historically been the standard of care for
9% 9% 6% 9% Other newly diagnosed nmHSPC and remains the preferred ADT across all stages.
90%
5% ADTs are used as single agents or in combination with a first-or second-
9% docetaxel-containing regimen generation anti-androgen therapy, particularly for Stage IV (M0) disease.
8%
80%
7% 13%
18% docetaxel, leuprolide + For patients receiving abiraterone, 58% receive generic abiraterone, with the
70%
12% remaining patients receiving a branded agent (Table 53)b
15% 5%
bicalutamide, goserelin
60% 13% + Docetaxel-containing regimens are used in 10-15% of nmHSPC patients.
5% 12% 19% bicalutamide, leuprolide
50%
Leuprolide with or without enzalutamide continues to be preferred in
15% 10% abiraterone, leuprolide the U.S. in this setting.
40% 10% 29%
enzalutamide, goserelin
30% 10% Regimen choice varies globally. Single-agent LHRHs are used as
enzalutamide, leuprolide initial treatment in 15-45% of patients with nmHSPC across all
20% 38% 7% regions, with lowest single-agent use in China and highest single
34%
26% Other LHRH monotherapy agent use in the U.S. and EU5. In Japan, LHRHs are primarily used in
10% combination with an anti-androgen therapy. U.S. physicians report
17%
leuprolide higher use rates for enzalutamide and abiraterone, while EU5,
0% Japanese, and Chinese physicians the prefer first-generation anti-
Stage I Stage II Stage III Stage IV androgen, bicalutamide. Docetaxel-based regimens are more
(M0) common in the EU5 and China compared to the U.S. and JP.
a) QP5.1 (n=29 Stage I, n=51 Stage II, n=86 Stage III, n=98 Stage IV (M0)): Of your hormone sensitive Stage I-IV(M0) prostate cancer patients with
local/locally advanced disease who receive systemic therapy as a part of initial therapy, what percent receive the following regimens? b) QP51B
(n=58): With regard to your administration of abiraterone, what percentage of the time do you administer abiraterone generic, Yonsa brand or Zytiga CancerMPact® Treatment Architecture U.S., Prostate Cancer 62
brand? Note: “Other” category includes various therapies used in <5% of patients each; Duration of therapy data is reported in the appendix.
âbiraterone includes steroid.
Non-metastatic HSPC disease recurrence patterns after initial therapy
Results of Initial Therapy by Stage, nmHSPC, U.S., 2023 (Table 14)*
Stage I 7% 9% 18% 16% 50%
Stage II 8% 11% 21% 22% 38%
Stage III 10% 17% 27% 20% 25%
Stage IV (M0) 15% 22% 35% 17% 11%
Refractory <1 year 1-5 years 5-10 years >10 years
+ Approximately 50% of patients with Stage I disease, 40% of patients with Stage II disease, and about 25% of patients with Stage III disease do
not relapse within ten years of initial therapy
+ For Stage IV (M0) patients, around 10% are disease free ten years after initial treatment, while 70% are refractory or relapse within five years.
*QP7 (n=90 Stage I, n=98 Stage II, n=102 Stage III, n=104 Stage IV (M0)): Of your hormone sensitive Stage I-IV (M0) prostate
cancer patients, what percent eventually developed a recurrence after initial therapy within the time frames listed below?
nmHSPC: Treatment Jump to Table 15, Table 16, and Table 17
Stages I–III patients are more likely to experience a biochemical recurrence after initial therapy,
while more advanced stage HSPC at initial diagnosis is more likely to recur as CRPC.
Type of First Recurrence by Initial Stage,
nmHSPC, U.S., 2023 (Table 15)a Stage of Local Recurrence by Initial Stage, nmHSPC,
100%
5%
U.S., 2023 (Table 16)b
6% 9%
Metastatic recurrence Stage
90% 8% 10% 20% 49% 51%
- become CRPC I
15% Stage
80% 13% II 44% 56%
16% Local recurrence
Stage
70% 6% 21% - become CRPC 39% 61%
16% III
13% 10% Percent (%) of Patients

60% Biochemical recurrence only
14% - become CRPC Recurrent disease equivalent to Stage I-III disease
50% 17% 15%
Recurrent disease equivalent to Stage IV (M0) disease
40%
20% - remain HSPC Time Between Newly Diagnosed Non-Metastatic Disease and
17%
Development of Metastatic Disease at First Recurrence by Stage,
30%
55% Local recurrence nmHSPC, U.S., 2023 (Table 17)c
20% 42% 14% - remain HSPC
10%
27%
Biochemical recurrence only
Stages I-III 24 months
13%
- remain HSPC
0%
Stage Stage Stage Stage IV
I II III (M0) Stage IV (M0) 20 months
a) QP8 (n=78 Stage I, n=94 Stage II, n=100 Stage III, n=102 Stage IV (M0)): Of your hormone sensitive Stage I-IV(M0) prostate patients who experience first
recurrence, what percent are biochemical (rising PSA and/or absolute PSA levels), radiographically confirmed local recurrences, or metastatic? b) QP9 (n=54
Stage I, n=68 Stage II, n=82 Stage III): Of your Stage I-III prostate patients who develop a radiographically-confirmed local recurrence, into which stage do they CancerMPact® Treatment Architecture U.S., Prostate Cancer 64
recur? c) QP18 (n=63 Stages I-III, n=63 Stage IV (M0)): Of your non-metastatic Stage I-IV(M0) prostate patients who developed metastatic disease at first
confirmed recurrence, what is the average duration of time (in months) that the patient remain non-metastatic before developing metastatic disease?
nmHSPC: Treatment Jump to Table 18 and Table 19
Systemic therapy with or without radiotherapy is primarily used to manage patients who
experience a local recurrence after initial therapy
Treatment Modality Used After First Local
Recurrence by Prior Therapy, + For locally recurrent disease, NCCN clinical guidelines recommend that for patients who
nmHSPC, U.S., 2023 (Table 18)a initially received radiotherapy, life expectancy should inform subsequent treatment
approaches. For patients with life expectancy <5 years, observation is recommended, while for
100% patients with life expectancy >5 years, PSA doubling time (PSADT) and prostate biopsy should
5% 9% Other be considered.1
10%
90% 7%
6% 6% + Physicians report that 65-70% of patients with recurrent disease receive systemic therapy,
Active Surveillance
80% 6% with systemic therapy only preferred.
8%
10% 16%
70% Observation / No + Around 10-15% of patients with recurrent disease will receive active surveillance or
therapy observation (no therapy).

9% 14%
60% Surgery ONLY
10%
50% 32% Observation / Active Surveillance as Initial Duration (Months)
RT ONLY
Management of First Local Recurrence, Prior to Active
40%
nmHSPC, U.S., 2023 (Table 19)b Therapy
Surgery, systemic
30% therapy
56%
49%
20%
34%
RT, systemic therapy Patients Under "Observation/No Therapy"
Who Eventually Receive Treatment 41% 13
10% Systemic therapy
only
0%
Radiotherapy Surgery Systemic
Patients Under "Active Surveillance" Who
Eventually Receive Treatment 55% 18
Therapy
Prior Therapy
a) QP11 (n=92 Post-Radiotherapy, n=87 Post-Surgery, n=74 Post-Systemic Therapy): Of your prostate cancer patients who experience their first biochemical or
radiographically confirmed local recurrence and remain hormone sensitive, what modalities do they receive as treatment for first-recurrence of disease? b) QP12 / QP13 (n=29
Observation / No therapy, n=31 Active Surveillance): What percent of your newly-recurrent hormone sensitive Stage I-IV (M0) prostate cancer patients who receive CancerMPact® Treatment Architecture U.S., Prostate Cancer 65
“Observation / No therapy” or “Active Surveillance” for first local recurrence eventually receive therapy? What is the average duration of “Observation / No therapy” and “Active
Surveillance” for your newly-recurrent hormone sensitive Stage I-IV (M0) prostate cancer patients who eventually receive therapy? 1. NCCN Guidelines Prostate v3.2023.
Leuprolide with or without enzalutamide is the preferred systemic therapy for first local
recurrence of nmHSPC
Systemic Therapy Utilization by Stage, nmHSPC

First Local Recurrence, U.S., 2023 (Table 20)* + Leuprolide remains the backbone of therapy for patients who
100% experience a first local recurrence of nmHSPC and is used in 75-80% of
10% 11% Other systemic therapy regimens for patients with Stages I–III and Stage IV
90% (M0) disease.
7% 6%
80% 6% 6% Other docetaxel-containing regimen
+ For patients receiving a combination therapy, physicians report a
10% preference for leuprolide combined with enzalutamide or abiraterone,
70% docetaxel, leuprolide which are both second-generation anti-androgen therapies.
21%
60% 12%
abiraterone, leuprolide
More physicians this year reported treating Stage IV (M0) with
50% 13% leuprolide combined with a second-gen anti-androgen therapy
21% bicalutamide, leuprolide
40% compared to single agent leuprolide.
30% 9% 29% enzalutamide, leuprolide

Choice of regimen varies globally. In the U.S. and EU5, many
20% physicians use LHRH agents with or without second-gen ARIs,
Other LHRH monotherapy with single agent leuprolide use highest in the U.S. (10-25%). In
10%
25% 6% Japan, LHRH agents are predominantly used in combination
8% leuprolide with bicalutamide. In China, docetaxel-based regimens,
0% bicalutamide-based regimens, and second-generation ADT with
Stages I-III Stage IV (M0) LHRH are all commonly used.
*QP14.1 (n=91 Stages I-III, n=65 Stage IV (M0)): Of your prostate cancer patients who experience their first biochemical or
radiographically confirmed local recurrence and remain hormone sensitive who receive systemic therapy for recurrent disease,
what percent receive the following regimens? Note: “Other” category includes various therapies used in <5% of patients each;
Duration of therapy data is reported in the appendix. âbiraterone includes steroid.
Non-metastatic HSPC disease recurrence patterns after therapy at first recurrence
Results of Therapy by Stage at First Recurrence, nmHSPC, U.S., 2023 (Table 21)*
Stages I-III 11% 17% 34% 19% 18%
Stage IV (M0) 17% 24% 33% 16% 11%
Refractory <1 year 1-5 years 5-10 years >10 years
+ Following therapy for first recurrence, most patients (> 80%) will experience a second recurrence within ten years.
+ Approximately 60% of Stage I–III patients and about 75% of Stage IV (M0) patients recur within five years.
*QP15 (n=98 Stages I-III, n=85 Stage IV (M0)): Of your hormone sensitive Stage I-IV(M0) prostate cancer patients who were
treated for a first non-metastatic recurrence, what percent eventually developed a second recurrence within the time frames listed CancerMPact® Treatment Architecture U.S., Prostate Cancer 67
below?
nmHSPC: Treatment Jump to Table 22, Table 23, and Table 24
For nmHSPC patients at second recurrence, around half of patients become CRPC
Type of Second Recurrence by Stage,

Stage of Second Local Recurrence,
nmHSPC, U.S., 2023 (Table 22)a
nmHSPC, U.S., 2023 (Table 23)b
100%
Local recurrence
14% 14%
90% - become CRPC Stages I-III at
First Recurrence 41% 59%
80%
15% Metastatic recurrence
27% - become CRPC
70% Percent (%) of Patients
60% 18% Biochemical recurrence only Recurrent disease equivalent to Stage I-III disease
- become CRPC Recurrent disease equivalent to Stage IV (M0) disease
50%
15%
13% Metastatic recurrence
40% - remain HSPC Time Between First Local Recurrence and Development of Metastatic
18%
30% 18% Disease at Second Recurrence by Stage, nmHSPC, U.S., 2023 (Table 24)c
Local recurrence
- remain HSPC
20% 15% Stages I-III 20 months
10% 22% Biochemical recurrence only
11% - remain HSPC
0%
Stages
I-III
Stage IV
(M0)
Stage IV (M0) 17 months
a) QP16 (n=94 Stages I-III, n=83 Stage IV (M0)): Of your hormone sensitive Stage I-IV(M0) prostate cancer patients who experience a second recurrence, what
percent of these recurrences are biochemical (rising PSA and/or absolute PSA levels), radiographically confirmed local recurrences, or metastatic? b) QP17 (n=74
Stages I-III): Of your Stage I-III prostate cancer patients who develop a second local recurrence, into which stage do they recur? c) QP18 (n=59 Stages I-III, n=59 CancerMPact® Treatment Architecture U.S., Prostate Cancer 68
Stage IV (M0)): Of your non-metastatic Stage I-IV(M0) prostate cancer patients who developed metastatic disease at second confirmed recurrence, what is the
average duration of time (in months) that the patient remain non-metastatic before developing metastatic disease?
Patients who experience a second local recurrence are primarily managed with systemic
therapy alone
Treatment Modality by Stage, Second Recurrent

nmHSPC, U.S., 2023 (Table 25)* + For nmHSPC patients experiencing a second recurrence, 75-80%
100% will receive systemic therapy. Systemic therapy alone is preferred
15% Other
in the majority of patients with Stage I-IV (M0) disease.
90% 17%
7%
+ Surgery and radiotherapy play limited roles in this setting.
80% 7%
RT ONLY
6% 5%
70% 5% Use of overall systemic therapy has remained consistent
15% since 2017.

60% 12% Surgery, RT, systemic therapy
50%
Treatment approaches are similar in the U.S., EU5, and
40% Surgery, systemic therapy Japan, with systemic therapy alone given to most patients
(55-70%). In China, modality use is more evenly distributed,
30% though systemic therapy (with or without RT) is still
54% 54% RT, systemic therapy preferred.
20%
10%
Systemic therapy only
0%
Stages I-III Stage IV (M0)
*QP19 (n=78 Stages I-III, n=57 Stage IV (M0)): Of your prostate cancer patients who have a second biochemical or
radiographically confirmed local recurrence and remain hormone sensitive, what modalities do they receive as treatment for second CancerMPact® Treatment Architecture U.S., Prostate Cancer 69
local recurrence of disease?
Second-generation anti-androgen therapies are commonly used for second local recurrence
Systemic Therapy Utilization by Stage, nmHSPC

Second Local Recurrence, U.S., 2023 (Table 26)*
100%
+ Second-generation anti-androgens plus an LHRH are the most common
5% Other treatment approach for patients with a second recurrence of disease, used in
6%
90% 9% 45-50% of patients, with enzalutamide plus leuprolide preferred.
6% Other first-gen ARI, docetaxel
5% + Traditional androgen-deprivation therapies (i.e., LHRHs) as a single agent
80% 7% 8% bicalutamide, leuprolide, docetaxel therapy (10-15%) or combined with a first-generation anti-androgen (10-
10% 15%) are used in around 25-30% of patients.
70% 7% Other first-gen ARI
5% 11% + Docetaxel is used in approximately 20-25% of regimens.

60% bicalutamide, leuprolide
11% 4%
50%
8% docetaxel, leuprolide Enzalutamide plus leuprolide has been the preferred regimen in this
7% setting for several years.
40% 6% Other single-agent LHRH
11% 8%
30% leuprolide In the U.S. and EU5, second-generation anti-androgen therapies
plus an LHRH are preferred over first-generation anti-androgen
Other second-gen ARI therapies plus an LHRH, whereas in China and Japan, more patients
20%
31% 31% are receiving first-generation anti-androgen therapies. In the U.S.,
10% EU5, and China, around 20-30% of patients receive a docetaxel-
enzalutamide, leuprolide containing regimen, while in Japan this number is only around 10%.
0%
*QP20.1 (n=69 Stages I-III, n=51 Stage IV (M0)): Of your prostate cancer patients who experience a second biochemical or
radiographically confirmed local recurrence and who remain hormone sensitive, and who receive systemic therapy for recurrent
disease, what percent receive the following regimens? Note: “Other” category includes various therapies used in <5% of patients CancerMPact® Treatment Architecture U.S., Prostate Cancer 70
each; Duration of therapy data is reported in the appendix. âbiraterone includes steroid.
Treatment:
Non-Metastatic
Castration-Resistant
Prostate Cancer
(nmCRPC)
nmCRPC: Treatment Jump to Table 27
Non-metastatic CRPC is primarily managed with systemic therapy only
Initial Treatment Modality by Stage,

nmCRPC, U.S., 2023 (Table 27)*
+ Castration-resistant prostate cancer (CRPC) is prostate cancer that progresses clinically,
radiographically, or biochemically despite castrate levels of serum testosterone (<50 ng/dL).
5%
5% + In the past, nmCRPC patients were more likely to undergo observation or active surveillance until
progression to metastatic disease, upon which patients would be eligible for metastatic CRPC
6%
treatment options. In 2018, two second-generation anti-androgen therapies, apalutamide and
enzalutamide, were approved for the treatment of nmCRPC. In 2019, darolutamide was also
10% approved in this setting.
+ Physicians now report around 80% of patients receive systemic therapy, with only around 10% of
59% patients receiving observation or active surveillance.
Utilization of systemic therapy has remained consistent after approval of agents indicated
for this disease setting.
Systemic therapy only

Utilization of systemic therapy is highest in Japan (92% of nmCRPC patients) with
RT, systemic therapy comparable systemic therapy use in U.S. (79%) and EU5 (77%). Chinese physicians report
Surgery, systemic therapy more evenly distributed single- and multimodal treatment approaches, although around
Active Surveillance 50% of patients will receive systemic therapy in this setting.
Observation / No therapy
*QP21 (n=96): Of your patients you see with non-metastatic CRPC diseases, what percent of patients are treated with each of the
modalities listed below as initial treatment for newly-developed non-metastatic CRPC disease? Note: “Other” category includes CancerMPact® Treatment Architecture U.S., Prostate Cancer 72
various therapies used in <5% of patients each.
nmCRPC: Treatment Return to Table of Contents
Clinical trial data that supported approvals in nmCRPC (i)

STRIVE SPARTAN
Trial
NCT01664923 NCT01946204
Trial arms enzalutamide bicalutamide enzalutamide bicalutamide apalutamide, ADT placebo, ADT
Sample size M0 + M1: 198 M0 + M1: 198 M0: 70 M0: 69 806 401
Geography U.S. U.S., EU, JP, ROW
Biomarker None None
Indication nmCRPC and mCRPC Non-metastatic, PSA doubling time ≤10 months
Metastasis-Free mPFS: 19.4 mos mPFS: 5.7 mos mPFS: Not reached mPFS: 8.6 mos 40.5 mos 16.2 mos
Survival
HR: 0.24, p<0.001 HR: 0.24, p<0.001 HR: 0.28, p<0.0001
Not reported Not reported Not reported Not reported 73.9 mos 59.9 mos
Overall Survival
Not reported Not reported HR: 0.784, p=0.0161
Total Grade 3/4 AEs 36% 36% Not reported Not reported 55.9% 36.4%
AE-related
8% 6% Not reported Not reported 15% 8.4%
Fatigue (5%), Fatigue (3%), Hypertension (16.3%), Hypertension (12.3%),
Most common Grade
Hypertension (5%), Hypertension (2%), Not reported Fall (2.7%), Fall (0.8%),
3/4 AEs*
Anemia (3%) Anemia (5%) Diarrhea (1.5%) Diarrhea (0.5%)
Smith, N Engl J Med, 2018; Small, J Clin Oncol, 2019;

Citation Penson, J Clin Oncol, 2016
Small, J Clin Oncol, 2020, Smith, Eur Urol, 2021
Clinical trial data that supported approvals in nmCRPC (ii)

PROSPER ARAMIS
Trial
NCT02003924 NCT02200614
Trial arms enzalutamide, ADT placebo, ADT darolutamide, ADT placebo, ADT
Sample size 933 468 955 554
Geography U.S., EU, ROW U.S., EU, JP, ROW
Biomarker None None
Indication Non-metastatic, PSA doubling time ≤10 months Non-metastatic, PSA doubling time ≤10 months
36.6 mos 14.7 mos 40.4 mos 18.4 mos

Metastasis-Free
Survival
HR: 0.29, p<0.0001 HR: 0.41, p<0.0001
67.0 mos 56.3 mos 3-yr OS: 83% 3-yr OS: 77%
Overall Survival
HR: 0.73, p=0.001 HR: 0.69, p=0.003
Total Grade 3/4 AEs 48% 27% 26.3% 21.7%
AE-related
9.4% 6.0% 8.9% 8.7%
Hypertension (4.6%), Asthenic Hypertension (3.5%), Hypertension (2.3%),

Most common Grade Hypertension (2.2%), Asthenic
conditions (4.0%), Coronary-artery disorder (2.0%), Coronary-artery disorder (0.4%),
3/4 AEs* conditions (0.9%), Fractures (1.7%)
Fractures (2.0%) Cardiac arrhythmias (1.8%) Cardiac arrhythmias (0.7%)
Citation Hussain, N Engl J Med, 2018; Sternberg, N Engl Med, 2020 Fizazi, N Engl J Med, 2019; Fizazi, N Eng J Med, 2020
Clinical trial data that supported approvals in nmCRPC (iii)

IMAAGEN
Trial
NCT01314118
Trial arms abiraterone, prednisone, ADT
Sample size 122
Geography U.S.
Biomarker None
Indication Non-metastatic, PSA doubling time ≤10 months
≥50% reduction in PSA during cycles 1-6: 86.9%

Response Rate
p<0.0001
Metastasis-Free
rPFS: 41.4 mos
Survival
Overall Survival Not reported
Total Grade 3/4 AEs 57%
AE-related
6.1%
Most common Grade hypertension (23.7%), hypokalemia (6.9%), peripheral

3/4 AEs* edema (1.5%)
Citation Ryan, J Urol, 2018
nmCRPC: Treatment Jump to Table 28, Table 29 and Table 53
Most patients with nmCRPC receive a second-generation anti-androgen therapy, with a

preference for enzalutamide
Initial Systemic Therapy
Utilization, nmCRPC, + Almost 85% of patients receive a second-generation anti-androgen as initial therapy for nmCRPC disease,
U.S., 2023 (Table 28)a with most U.S. physicians preferring enzalutamide (39%). Abiraterone (plus prednisone) is also used in 18%
of patients despite abiraterone lacking a formal approval in this setting. For patients receiving abiraterone,
100%
55% of patients receive generic abiraterone (Table 53).c
11%
90% Other
+ For patients with CRPC, guidelines recommend castrate levels of testosterone (<50ng/dL) be maintained by
5%
continuing an LHRH while an additional therapy is applied. Physicians report 80% of nmCRPC patients
80%
11% continue to receive androgen deprivation therapy (ADT) concurrent with initial treatment.
docetaxel ± prednisone
70%
15% Treatment patterns have remained consistent since 2019.

60%
apalutamide
50%
Second-gen ARIs are preferred across all regions, though preference varies. Enzalutamide is
18% preferred in the U.S. while darolutamide or apalutamide are preferred in the EU5. In Japan,
40% darolutamide darolutamide is common while Chinese physicians prefer abiraterone.
30% Utilization of ADT Concurrent with Initial Therapy,

abiraterone, prednisone nmCRPC, U.S., 2023 (Table 29)b
20% 39%
10% 80% 20%

enzalutamide
0%
Initial Therapy Receive concurrent ADT Do not receive concurrent ADT
a) QP25.1 (n=87): Of your nmCRPC patients who receive systemic therapy as part of their initial treatments for newly-developed nmCRPC disease,
what percent receive the following systemic regimens? b) QP25A (n=87): Of your patients who receive systemic therapy for the treatment of nmCRPC,
what percent continue androgen deprivation therapy (ADT) concurrent with the regimens selected in the previous question? c) QP51B (n=33): With CancerMPact® Treatment Architecture U.S., Prostate Cancer 76
regard to your administration of abiraterone, what percentage of the time do you administer abiraterone generic, Yonsa brand or Zytiga brand? Note:
“Other” category includes various therapies used in <5% of patients each; Duration of therapy data is reported in the appendix.
nmCRPC: Treatment Jump to Table 30, Table 31, and Table 32
Disease recurrence patterns after initial therapy for nmCRPC
Results of Initial Therapy, nmCRPC, U.S., 2023 (Table 30)a
Refractory
<1 year
Initial Therapy 12% 25% 42% 21%
1-5 years
>5 years
Location of Recurrence (Table 31)b
Time Between Newly Diagnosed

nmCRPC and Development of
+ The majority of nmCRPC patients are 64% Metastatic Disease (Table 32)c
Metastatic
refractory or recurrent within five years of recurrence
19 months
initial therapy.
+ Metastatic recurrence occurs in nearly 65% Local recurrence

of nmCRPC patients who recur.
36%
nmCRPC
a) QP26 (n=98): Of your newly-developed nmCRPC patients who were treated for nmCRPC disease, what percent eventually recurred again within the
time frames listed below? b) QP27 (n=96): Of your prostate cancer patients who were treated initially for newly-developed nmCRPC disease and who
experienced another recurrence, what percent recurred again with local or metastatic disease? c) QP28 (n=96): Of your nmCRPC patients who were CancerMPact® Treatment Architecture U.S., Prostate Cancer 77
initially treated for newly-developed nmCRPC disease, and who later recurred with metastatic disease, what is the duration of time that the patients
remain nmCRPC before developing metastatic disease?
Treatment:
Metastatic Hormone
Sensitive Prostate
Cancer
(mHSPC)
mHSPC: Treatment Jump to Table 33 and Table 34
Over half of metastatic patients are recurrent from non-metastatic disease; among mHSPC
patients, systemic therapy is the most common treatment modality
Sources of Metastatic Patients, U.S., 2023 Initial Treatment Modality, mHSPC, U.S., 2023
(Table 33)a (Table 34)b
100%
Newly diagnosed metastatic

90% 20%

80% Other
patients
29% 70% 12%
60%
41%
Metastatic HSPC patients who 50% RT, systemic therapy
recur from non-metastatic disease 40%
30%
68%
20%
Metastatic CRPC patients who Systemic therapy only
10%
30% recur from non-metastatic disease
0%
mHSPC
+ Approximately 90% of mHSPC patients receive systemic therapy as an initial therapy, alone or with another modality.
+ About 60% of metastatic HSPC or CRPC patients recurred from non-metastatic disease while around 40% of metastatic patients have de novo disease
Systemic therapy is the preferred treatment modality across regions.

There has been minimal change in the treatment modalities used with Physicians in Japan are more likely to use systemic therapy only (81%)
mHSPC patients over the last few years. compared to the U.S. (68%), EU5 (66%) or CN (22%). In Japan, where
routine screening practices are not as heavily encouraged, the majority of
patients are de novo metastatic patients compared to the U.S., CN and
EU5, where approximately one-third of patients are de novo metastatic.
a) QP29 (n=108): Of your patients with metastatic prostate cancer, what percent are newly diagnosed as Stage IV (M1)? What
percent have recurred to metastatic disease after being initially diagnosed with an earlier stage of disease? b) QP30 (n=109): Of
patients that you see with hormone sensitive Stage IV (M1) prostate cancer, approximately what percent of patients are treated
with each of the modalities listed below? Note: “Other” category includes various therapies used in <5% of patients each.
mHSPC: Treatment Return to Table of Contents
Clinical trial data that supported approvals in mHSPC (i)

Italian Prostatic Cancer Project (PONCAP) Study
Trial INT 0036 International Anandron Study Group
Group
orchiectomy 
Trial arms flutamide, leuprolide placebo, leuprolide goserelin, flutamide goserelin orchiectomy  nilutamide
placebo
Sample size 303 300 187 186 225 232
Geography U.S. EU EU
Locally advanced Stage C or metastatic Stage D; no

Indication Untreated, Stage D2 with bone or visceral metastasis Stage D2 metastatic HSPC
previous orchiectomy, hormones or cytotoxic therapy
Progression- Free 16.5 mos 13.9 mos TTP: 24.0 mos TTP: 18.0 mos 21.2 mos 14.7 mos
Survival p=0.039 p=0.09 p=0.0024
35.6 mos 28.3 mos 34.0 mos 32.0 mos 27.3 mos 23.6 mos
Overall Survival
p=0.035 p=0.40 p=0.0326
AE-related
Not reported Not reported Not reported Not reported 7 pts (3%) 8 pts (4%)
Any Grade Any Grade
Any Grade Any Grade Transaminase increase Transaminase increase
Most common Grade Hot flashes (63.6%), Hot flashes (60.8%), (12.0%) (2.6%)
3/4 AEs* Diarrhea (13.6%), Diarrhea (4.9%), Gastrointestinal toxicity Gastrointestinal toxicity
Gynecomastia (13.3%) Gynecomastia (12.7%) (12.0%) (0.6%)
Skin rash (3.3%) Skin rash (1.2%)
Citation Crawford, N Engl J Med, 1989 Boccardo et al., Eur J Cancer, 1993 Dijkman, J Urol, 1997
Clinical trial data that supported approvals in mHSPC (ii)

Trial CASODEX Combination Study group Italian Leuprorelin Group SWOG-8894 / INT-0105
LHRH-A,
Trial arms LHRH-A, bicalutamide flutamide, leuprolide leuprolide orchiectomy flutamide orchiectomy placebo
flutamide
Sample size 404 409 121 120 697 685

Geography U.S., EU EU U.S.
Indication Stage D2 metastatic HSPC Previously untreated Stage C or D metastatic and antiandrogen naïve (HSPC)
Progression- Free 97 weeks 77 weeks TTP: 20.0 mos TTP: 19.4 mos 20.4 mos 18.6 mos
Survival
HR: 0.85, p=0.092 p=0.64 p=0.26
180 weeks 148 weeks 32.1 mos 31.6 mos 33.5 mos 29.9 mos
Overall Survival
HR: 0.85, p=0.095 p=0.83 HR: 0.91, p=0.14
AE-related
10% 16% Not reported Not reported 33 pts (5%) 10 pts (2%)
≥ Grade 2 ≥ Grade 2
Any Grade Any Grade
Most common Grade Hot flashes (10.3%), Hot flashes (9.7%),
Hot flashes (53%), Pain Hot flashes (53%), Pain Not reported Not reported
3/4 AEs* Anemia (8.5%), Diarrhea Anemia (5.4%), Diarrhea
(31%), Diarrhea (12%) (35%), Diarrhea (26%)
(6.3%) (2.7%)
Citation Schellhammer, Urology, 1997 Bono, Urol Int, 1998 Eisenberger, N Engl J Med, 1998
Clinical trial data that supported approvals in mHSPC (iii)

SWOG-9346 / INT-0162 E3805 / CHARRTED GETUG 12
Trial
NCT00002651 NCT00309985 NCT00055731
docetaxel, estramustine,
Trial arms continuous ADT intermittent ADT docetaxel, ADT ADT alone ADT alone
ADT
Sample size 765 770 397 393 207 206
Geography U.S., EU, ROW U.S. EU
Newly diagnosed metastatic HSPC, ECOG 0-2, PSA≥ Treatment naive Stage T3–T4, Gleason score of ≥8,
Indication Metastatic HSPC
5ng/mL PSA >20 ng/mL, or pathological node-positive
12-yr RFS: 49.4% 12-yr RFS: 36.3%
NR NR TTP: 33.0 mos TTP: 19.8 mos
Progression Free mRFS: 11.6 mos mRFS: 8.1 mos
Survival
NR HR: 0.62, p<0.001 HR: 0.71, p=0.0109
5.8 years 5.1 years 57.6 mos 47.2 mos 12-yr: 88.2% 12-yr: 83.9%
Overall Survival
Non-inferiority HR: 1.11 HR: 0.72, p=0.0018 HR: 0.70, p=0.0109
Total Grade 3/4 AEs 32.7% 30.4% 29.3% Not reported ≥Grade 2: 21% ≥Grade 2: 18%
AE-related
Long term Long term
Neutropenia (12.1%),
Most common Grade NR; Patient reported impotence rates, libido and Genitourinary (2%), Genitourinary (2%),
Febrile neutropenia Not reported
3/4 AEs* mental health favored intermittent group Bowel-colon (1%), Bowel-colon (0%),
(6.1%), Fatigue (4.1%)
Rectum-anus (1%) Rectum-anus (3%)
Sweeney, N Engl J Med, 2015; Kyriakopoulos, J Clin
Citation Hussain, N Engl J Med, 2013 Fizazi, Lancet Oncol, 2015; Fizazi, Ann Oncol, 2018
Oncol, 2018
have a stipulated primary endpoint per-protocol. Please refer to Appendix (Table A.1) for definitions of abbreviations. 1. Findings
were statistically inconclusive and could not rule out a 20% greater risk of death with intermittent therapy than with continuous
therapy. *Shown are the top 3 Grade 3/4 adverse events reported for the experimental arm or arm with the highest efficacy.
Clinical trial data that supported approvals in mHSPC (iv)

STAMPEDE
Trial
NCT00268476
Trial arms docetaxel, zoledronic acid, ADT zoledronic acid, ADT docetaxel, ADT ADT alone (SOC)
Sample size 593 593 592 1184
Geography EU
Biomarker None
Indication Newly diagnosed metastatic node positive or high-risk locally advanced
mFFS: 36 mos mFFS: 22 mos mFFS: 37 mos mFFS: 20 mos

Progression-Free
Survival HR: 0.62, p<0.0001 versus SOC HR: 0.92, p=0.198 versus SOC HR: 0.61, p<0.0001 versus SOC -
76 mos NR 81 mos 71 mos

Overall Survival
HR: 0.82, p=0.022 versus SOC HR: 0.94, p=0.450 versus SOC HR: 0.78, p=0.006 versus SOC -
Total Grade 3/4 AEs 52% 32% 52% 32%
AE-related
12% 7% Not reported Not reported
Most common Grade Febrile neutropenia (14%), Neutropenia Febrile neutropenia (<1%), Neutropenia Febrile neutropenia (15%), Neutropenia Febrile neutropenia (14%), Neutropenia
3/4 AEs* (12%), GI disorder (7%) (<1%), GI disorder (3%) (12%), GI disorder (7%) (12%), GI disorder (7%)
Citation James, Lancet, 2016
Clinical trial data that supported approvals in mHSPC (v)

STAMPEDE
Trial
NCT00268476
Trial arms abiraterone, prednisone, ADT ADT only abiraterone, prednisone, ADT ADT only
Sample size 960 (M0 + M1) 957 (M0 + M1) 502 (M1) 500 (M1)
Geography EU
Biomarker None
Indication Newly diagnosed metastatic node positive or high-risk locally advanced
3-yr FFS: 75% 3-yr FFS: 45% mPFS: 55 mos; mPFS: 24 mos;
Progression-Free Mean FFS: 43.9 Mean FFS: 30.0 5-yr FFS: 45% 5-yr FFS: 13%
Survival*
HR: 0.29, p<0.0001 HR: 0.34; p<0.0001
3-yr OS: 83% 3-yr OS: 76% mOS: 77 mos; 5-yr OS: 60% mOS: 46 mos; 5-yr OS: 41%
Overall Survival
HR: 0.63, p<0.001 HR: 0.62, p<0.0001
Total Grade 3/4 AEs 47% 33% Grade 3-5: 54% Grade 3-5: 38%
AE-related
Endocrine disorder (14%), Endocrine disorder (14%),

Most common Grade
Cardiovascular disorders (10%), Cardiovascular disorders (4%), Not reported Not reported
3/4 AEs**
Musculoskeletal disorders (7%) Musculoskeletal disorders (5%)
Citation James, N Engl J Med, 2017; James, Int J Cancer, 2022; Attard, Lancet Oncology, 2023
have a stipulated primary endpoint per-protocol. Please refer to Appendix (Table A.1) for definitions of abbreviations. *Secondary
endpoint of Failure-Free Survival (FFS) is the time from initiation of treatment to the first progression event.
**Shown are the top 3 Grade 3/4 adverse events reported for the experimental arm or arm with the highest efficacy.
Clinical trial data that supported approvals in mHSPC (vi)

LATITUDE ARASENS PEACE-1
Trial
NCT01715285 NCT02799602 (NCT01957436)
abiraterone, prednisone, darolutamide + ADT + Placebo + ADT + abiraterone + ADT + ADT

Trial arms placebos, ADT
ADT docetaxel docetaxel docetaxel ± RT + docetaxel ± RT
Sample size 597 602 651 654 583 589
Geography U.S., EU, JP, ROW U.S., EU, JP, CN, ROW EU, ROW
Indication Newly-diagnosed mHSPC mHSPC mHSPC
Progression-Free rPFS: 33.0 mos rPFS: 14.8 mos NR NR rPFS: 4.5 yrs rPFS: 2.2 yrs
Survival* HR: 0.47, p<0.001 NR HR 0.54 (99⋅9% CI, 0⋅41 to 0⋅71), p<0.001
Not estimable 48.9

53.3 mos 36.5 mos 5.7 yrs 4.7 yrs
Overall Survival 4-yr OS: 62.7% 4-yr OS: 50.4%
HR: 0.66, p<0.0001 HR: 0.68, p<0.001 HR 0.82 (95⋅1% CI, 0⋅69 to 0⋅98), p=0.03
Total Grade 3/4 AEs 63% 48% 66.1% 63.5% 63% 52%
AE-related
12% 10% 13.5% 10.6% 17% 21%
neutropenia (33.7%),
Hypertension (21%), Hypertension (10%), neutropenia (34.2%), hypertension (22%) hypertension (13%)
Most common Grade febrile neutropenia
Hypokalemia (12%), Hypokalemia (2%), febrile neutropenia neutropenia (10%) neutropenia (9%)
3/4 AEs** (7.8%), hypertension
hepatotoxicity (8%) hepatotoxicity (3%) (7.4%), anemia (5.1%) hepatotoxicity (6%) hepatotoxicity (1%)
(6.4%)
Fizazi, N Eng J Med, 2017; Fizazi, J Clin Oncol, 2018;

Citation Smith, NEJM, 2022 Fizazi, Lancet, 2022
Fizazi, Lancet Oncol, 2019
have a stipulated primary endpoint per-protocol. Please refer to Appendix (Table A.1) for definitions of abbreviations. *Secondary
endpoint of Failure-Free Survival (FFS) is the time from initiation of treatment to the first progression event.
**Shown are the top 3 Grade 3/4 adverse events reported for the experimental arm or arm with the highest efficacy.
Clinical trial data that supported approvals in mHSPC (vii)

TITAN ENZAMET ARCHES
Trial
NCT02489318 NCT02446405 NCT02677896
Trial arms apalutamide, ADT placebo, ADT enzalutamide, ADT placebo, ADT enzalutamide, ADT placebo, ADT
Sample size 525 527 563 562 574 576
Geography U.S., EU, JP, CH, ROW U.S., EU, ROW U.S., EU, JP, ROW
de novo or after recurrence from prior local therapy

Indication mHSPC 1L mHSPC
mHSPC
Progression-Free rPFS: Not Reached rPFS: 22.1 mos 3-yr EFS: 68% 3-yr EFS: 41% rPFS: Not reached rPFS: 19.45mos
Survival HR: 0.48, p<0.0001 HR: 0.40, p<0.001 HR: 0.39, p<0.001
OS 4-yr: 65% OS 4-yr: 52% OS 5-yr: 67% OS 5-yr: 57% Not reached Not reached
Overall Survival
HR: 0.65, p<0.0001 HR: 0.67, p=0.002 HR: 0.66, p=0.001
Total Grade 3/4 AEs 42.2% 40.8% 56% 42% 24.3% 25.6%
AE-related
8.0% 5.3% 5.9% 2.5% 7.2% 5.2%
Hypertension (3.3%), Hypertension (1.7%),

Hypertension (8.4%), Hypertension (9.1%), Hypertension (8%), Hypertension (4%),
Most common Grade Fatigue (1.7%), Fatigue (1.7%),
Rash (6.3%), Back pain Rash (0.6%), Back pain Febrile neutropenia (7%), Febrile neutropenia (6%),
3/4 AEs* Musculoskeletal events Musculoskeletal events
(2.3%) (2.7%) Neutropenia (6%) Neutropenia (3%)
(1.6%) (2.1%)
Davis, N Engl J Med, 2019 Armstrong, J Clin Oncol, 2019; Armstrong, J Clin
Citation Chi, N Engl J Med, 2019; Chi, J Clin Oncol, 2021
Sweeney, Lancet, 2023 Oncol, 2022
Clinical trial data that supported approvals in mHSPC (viii)

HERO
Trial
NCT03085095
Trial arms relugolix leuprolide
Sample size 622 308
Patient Segment Stage III-IV androgen-sensitive
96.7% 88.8%
Sustained Castration
Rate
95% CI: 94.9 to 97.9, P<0.001
79.4% 19.8%
PSA response
(day 15)
P<0.001
Total Grade 3/4 AEs 18% 20.5%
AE-related
NR NR
Hypertension (1.6%) Hypertension (0.6%)

Most common Grade Hot flash (0.6%) Hot flash (0%)
3/4 AEs* Fatigue (0.3%) Fatigue (0%)
Arthralgia (0.3%) Arthralgia (0%)
Citation Shore, N Eng J Med, 2020
FIRST-LINE SYSTEMIC THERAPY: Second-generation anti-androgen in combination with

LHRH agents are preferred for first-line mHSPC patients
Initial Systemic Therapy Utilization,

mHSPC, U.S., 2023 (Table 35)a + Enzalutamide with leuprolide is utilized in about one-quarter of metastatic
100% HSPC patients. Other second-generation ARIs, abiraterone and apalutamide,
11% Other are also commonly used in mHSPC.
90%
6% leuprolide + Of mHSPC patients receiving abiraterone, 60% of patients receive generic
80% 6% abiraterone, with the remaining patients receiving branded agents (Table 53)b
docetaxel, leuprolide
8% + Traditional hormone agents (i.e. LHRH agents ± first-generation anti-

70%
7% androgens) continue to be commonly used, with over 20% utilization.
Other ARI + LHRH + docetaxel
60%
8% + Around 25% of patients will receive docetaxel in this setting. Two trials,
abiraterone + LHRH + docetaxel
ARASENS and PEACE-1, have now shown the benefit of adding docetaxel to
50% 7%
LHRH and a second-gen ARI, for first line mHSPC.
bicalutamide, leuprolide
40%
8%
Other LHRH + second-gen ARI ± prednisone Enzalutamide + leuprolide remains the most commonly used
30% 13%
approach in this setting, though use of docetaxel increased compared
apalutamide, leuprolide to previous years
20%
25% abiraterone, leuprolide

10%
Second-generation anti-androgen regimens plus LHRH agents are
enzalutamide, leuprolide preferably utilized in the U.S. and EU5. In Japan and China, LHRH
0%
First-Line agents are combined with first or second-generation anti-androgen
therapies.
a) QP31.1 (n=105): Of your hormone sensitive Stage IV (M1) prostate cancer who receive systemic therapy as initial therapy for metastatic disease,
what percent receive the following regimens? b) QP51B (n=63): With regard to your administration of abiraterone, what percentage of the time do you
administer abiraterone generic, Yonsa brand or Zytiga brand? Note: “Other” category includes various therapies used in <5% of patients each; CancerMPact® Treatment Architecture U.S., Prostate Cancer 88
Duration of therapy data is reported in the appendix. âbiraterone includes steroid.
mHSPC: Treatment Jump to Table 36
SECOND-LINE SYSTEMIC THERAPY: The majority of patients are treated with enzalutamide-
and abiraterone-based regimens
Second-Line Systemic Therapy Utilization,

mHSPC, U.S., 2023 (Table 36)*
+ Enzalutamide- and abiraterone-based regimens are used in
100% around 50% of mHSPC patients in the second-line, while
11% Other apalutamide-based regimens are used in around 12% of patients
90%
8% Other LHRH + docetaxel ± 1st-gen ARI + Around 30% of patients will receive docetaxel as part of their
80%
5%
abiraterone, prednisone, leuprolide, docetaxel
second-line therapy, with half receiving a second-gen ARI + LHRH +
70%
7% docetaxel combination.
8% darolutamide + LHRH + docetaxel

60%
5% Like in first line, a second-gen ARI + a LHRH is the
docetaxel, leuprolide
50% standard of care, but use of docetaxel has been increasing.
13%
1st-gen ARI + LHRH
40%
9% 2nd-gen ARI + LHRH Treatment patterns are similar across regions, with the
30% majority of patients treated with second-generation ARIs,
13% apalutamide, leuprolide enzalutamide or abiraterone. In China, the EU, and the U.S.
20% docetaxel-based regimens are also commonly used (~30-
37% of patients) while use is lower in the Japan (~20%).
10% 20%
enzalutamide, leuprolide
0%
Second-Line
*QP34.1 (n=94): Of your hormone sensitive Stage IV (M1) prostate cancer who receive second-line systemic therapy for hormone
sensitive disease, what percent receive the following regimens? Note: “Other” category includes various therapies used in <5% of CancerMPact® Treatment Architecture U.S., Prostate Cancer 89
patients each; Duration of therapy data is reported in the appendix. âbiraterone includes steroid.
Approximately 20% of mHSPC patients who receive first-line therapy go on to receive second-
line therapy, with rates decreasing through third-line therapy
Metastatic HSPC Patients Who Receive Later Lines of Systemic Therapy, U.S., 2023 (Table 37)a
1L Drug-Treated
mHSPC
100% First-Line
Progressed and Progressed and

In long term Died before remained hormone remained hormone
Progressed and
response – no received next line of sensitive but did not sensitive and
became CRPC
further therapy therapy receive next line of received 2L
therapy systemic therapy Second-Line
17.5% 13.4% 14.6% 34.0% 20.6%
Progressed and Progressed and

In long term Died before remained hormone remained hormone
Time Between Initial Treatment response – no received next line of sensitive but did not
Progressed and
sensitive and Third-Line
became CRPC
for mHSPC and Becoming further therapy therapy receive next line of
therapy
received 3L
systemic therapy
mCRPC (Table 38)b 12.5% 17.6% 13.2% 41.6% 15.1%
17 months
+ There is significant unmet need for alternative treatment options that can extend long-term survival, particularly in later-line therapy for mHSPC patients, as
evidenced by the low proportions of patients who achieve long-term response or progress and are able to receive second- or third-line therapy.
+ One-third of first-line and ~40% of second-line metastatic patients eventually fail hormone therapy and become castration-resistant.
a) QP32 / QP35: What are the treatment outcomes of your patients who receive first-line (n=105) / second-line (n=95) systemic
therapy for hormone sensitive metastatic prostate cancer? b) QP36 (n=96): Of your metastatic hormone sensitive prostate cancer
patients who were treated for their metastatic disease but recurred with CRPC, what is the average duration of time (in months) that
these metastatic patients remain hormone sensitive before becoming CRPC?
Click for Table
Return to TableofofContents
Contents
mHSPC: Treatment Jump to Table 39
Physicians report over 55% ORR and PFS over 1.5 years for initial treatment of mHSPC, but
response rates and PFS decrease with each line of therapy
Results by Line of Therapy, mHSPC, U.S., 2023 (Table 39)
Response Ratesa Progression-Free Survivalb
Initial Treatment 22% 35% 20% 21.6
Treatment for Recurrent Disease 14% 33% 18% 12.6
Complete response rate Partial response rate Stable disease PFS (months)
CR + PR = Objective Response Rate (ORR)
a) QP37 (n=105 initial treatment, 95 recurrent): Of your hormone sensitive metastatic Stage IV (M1) prostate cancer patients who
receive systemic therapy for treatment, please estimate the response rates to therapy.
b) QP38 (n=105 initial treatment, 95 recurrent): Of your hormone sensitive metastatic Stage IV (M1) prostate cancer patients who
receive systemic therapy for treatment, please estimate the average PFS of these patients after therapy.
Treatment:
Metastatic
Castration Resistant
Prostate Cancer
(mCRPC)
mCRPC: Treatment Jump to Table 40, Table 41 and Table 42
Physicians rely primarily on systemic therapy for both symptomatic and asymptomatic
patients with mCRPC
Symptomology Among mCRPC Patients,

First-Line Treatment Modality, mCRPC,
U.S., 2023 (Table 41)b
U.S., 2023 (Table 42)c
100%
90% 17% 17%

Asymptomatic mCRPC Other
80% 7% 7%
50% 50%
70% 10% 13%

Symptomatic mCRPC
60% Surgery, systemic therapy
50%
40%
RT, systemic therapy
66% 63%
30%
+ Populations of mCRPC patients are split between asymptomatic and
symptomatic disease at first mCRPC presentation. 20%
+ Similar to mHSPC, mCRPC patients predominantly receive initial systemic 10% Systemic therapy only
therapy to treat their disease.
0%
+ 57% mCRPC patients previously received an ARI prior to their disease Asymptomatic Symptomatic
becoming metastatic CRPC (Table 40)a mCRPC mCRPC
a) QP39A (n=109): What percentage of your patients with mCRPC disease received an androgen receptor inhibitor (ARI) prior to their disease
becoming mCRPC? b) QP39 (n=109): What percentage of your patients with mCRPC diseases are symptomatic versus asymptomatic at the time
when they first present mCRPC disease? c) QP40 (n=103 asymptomatic, n=105 symptomatic): Of your metastatic patients who newly became CRPC, CancerMPact® Treatment Architecture U.S., Prostate Cancer 93
approximately what percent of patients are treated with each of the modalities listed below as initial treatment for mCRPC disease?
mCRPC: Treatment Return to Table of Contents
Clinical trial data that supported approvals in first-line mCRPC (i)

SWOG 9916
Trial TAX 327
NCT00004001
docetaxel docetaxel
docetaxel
Trial arms mitoxantrone, prednisone (30 mg/m2 QW), prednisone (75 mg/m2 Q3W), prednisone mitoxantrone, prednisone (MP)
(60 mg/m2 Q3W), estramustine
(D1P) (D3P)
Sample size 338 336 334 335 337
Geography U.S. U.S., EU, ROW
mCRPC, no prior estramustine, taxane, anthracycline,
Indication mCRPC, no prior cytotoxic agents (except estramustine)
mitoxantrone
50% 27% 48% 45% 32%
PSA Response Rate
p<0.001 D3P vs MP - p<0.001; D1P vs MP - p<0.001
Radiographic 6.3 mos 3.2 mos NR NR NR

Progression Free
Survival p<0.001 NR
17.5 mos 15.6 mos 17.8 mos 19.2 mos 16.3 mos
Overall Survival
HR: 0.80, p=0.02 D3P vs MP - HR: 0.79, p=0.004; D1P vs MP - HR: 0.87, p=0.086
Total Grade 3/4 AEs 55.8% 34.5% 29% 26% 20%
AE-related
16% 10% 5% 3% 3%
Nausea and vomiting (20%), Nausea and vomiting (5%),
Most common Grade Neutropenia (2%), Anemia Neutropenia (32%), Anemia Neutropenia (22%), Anemia
Hematologic (19%), Hematologic (16%),
3/4 AEs* (5%), Fatigue (5%) (5%), Fatigue (5%) (2%), Fatigue (5%)
Cardiovascular (14%) Cardiovascular (7%)
Citation Petrylak, N Eng J Med, 2004 Tannock, N Eng J Med, 2004; Berthold, J Clin Oncol, 2008
Clinical trial data that supported approvals in first-line mCRPC (ii)

IMPACT COU-AA-302
Trial
NCT00065442 NCT00887198
Trial arms sipuleucel-T placebo abiraterone, prednisone placebo, prednisone
Sample size 341 171 546 542
Geography U.S., ROW U.S., EU, ROW
Indication mCRPC, no prior chemotherapy in 80% sipuleucel-T and 85% placebo pts Asymptomatic/mildly symptomatic, chemotherapy naïve, mCRPC
≥ 50% decline: 2.6% ≥ 50% decline: 1.3% > 50% decline: 62% > 50% decline: 24%
PSA Response Rate
NR p<0.001
Radiographic NR NR 16.5 mos 8.3 mos

Progression Free
Survival NR HR: 0.53, P<0.001
25.8 mos 21.7 mos 34.7 mos 30.3 mos

Overall Survival
HR: 0.78, p=0.03 HR: 0.81, p=0.0033
Total Grade 3/4 AEs 31.7% 35.1% 54% 44%
AE-related
Not reported Not reported 13% 10%
Most common Grade Back pain (3.6%), Arthralgia (2.1%), Back pain (4.8%), Arthralgia (3.0%), Fatigue (39%), Back pain (32%), Fatigue (34%), Back pain (32%),
3/4 AEs* Asthenia (1.8%) Asthenia (1.2%) Arthralgia (28%) Arthralgia (24%)
Citation Kantoff, N Eng J Med, 2010 Ryan, N Eng J Med, 2013; Ryan, Lancet Oncol, 2015
Clinical trial data that supported approvals in first-line mCRPC (iii)

PREVAIL
Trial
NCT01212991
Trial arms enzalutamide placebo
Sample size 872 845
Patient Segment mCRPC with PSA or radiographic progression on ADT
≥50% decline: 78.0% ≥50% decline: 3.5%
PSA Response Rate
p<0.001
Median Time to PSA 11.2 mos 2.8 mos

Progression HR: 0.17, P<0.001
Not reached 3.9 mos
Radiographic Investigator assessed: Investigator assessed:
Progression Free 20.0 mos 5.4 mos
Survival HR: 0.19, P<0.001
Investigator assessed: HR: 0.32, p<0.0001
3yr: 32.4 mos 3yr: 30.2 mos
Overall Survival
HR: 0.71, P<0.001
Total Grade 3/4 AEs Grade ≥3: 53% Grade ≥3: 38%
AE-related
9.1% 6.0%
Most common Grade Hypertension (8.7%), Fractures (4.8%), Fatigue Hypertension (2.7%), Fractures (2.0%), Fatigue
3/4 AEs* (4.1%) (3.0%)
Citation Beer, N Engl J Med, 2014; Beer, Eur Urol, 2017; Armstrong, Eur Urol, 2020
Clinical trial data that supported approvals in first-line mCRPC (iv)

STRIVE TERRAIN
Trial
NCT01664923 NCT01288911
Trial arms enzalutamide bicalutamide enzalutamide bicalutamide enzalutamide bicalutamide
Sample size M0 + M1: 198 M0 + M1: 198 M1: 128 M1: 129 184 191
Geography U.S. U.S., EU, ROW
Indication nmCRPC and mCRPC asymptomatic or minimally symptomatic mCRPC
> 50% decline: 81% > 50% decline: 31% > 50% decline: 76% > 50% decline: 25%
> 50% decline: 82% > 50% decline: 21%
PSA Response Rate > 90% decline: 65% > 90% decline: 9% > 90% decline: 59% > 90% decline: 7%
> 50% & > 90% decline: p<0.001, each > 50% & > 90% decline: p<0.001, each p<0.001
Radiographic Not reached 11.2 mos Not reached 8.3 mos mPFS: 15.7 mos mPFS: 5.8 mos
Progression Free
Survival HR: 0.30, p<0.001 HR: 0.32, p<0.001 HR: 0.44, p<0.0001
Overall Survival
Not reported Not reported Not reported
Total Grade 3/4 AEs 36% 36% Not reported Not reported 40% 38%
AE-related
8% 6% Not reported Not reported 8% 5%
Fatigue (5%), Fatigue (3%),
Most common Grade Hypertension (7%), Back Hypertension (7%), Back
Hypertension (5%), Hypertension (2%), Not reported
3/4 AEs* pain (3%), Fracture (3%) pain (2%), Fracture (1%)
Anemia (3%) Anemia (5%)
Citation Penson, J Clin Oncol, 2016 Shore, Lancet Oncol, 2016
Clinical trial data that supported approvals in first-line mCRPC (v)

FIRSTANA
Trial
NCT01308567
Trial arms cabazitaxel 20 mg/m2 (C20) cabazitaxel 25 mg/m2 (C25) docetaxel 75 mg/m2 (D75)
Sample size 389 388 391

Geography U.S., EU, JP, CH, ROW
Indication chemotherapy naive mCRPC
> 50% decline: 60.7% > 50% decline: 68.7% > 50% decline: 68.4%
PSA Response Rate
C20 versus D75 - p=0.052; C25 versus D75 - p=0.999
Radiographic mPFS: 4.4 mos mPFS: 5.1 mos mPFS: 5.3 mos
Progression Free
Survival C20 versus D75 - HR: 1.06, p=0.422; C25 versus D75 - HR: 0.99, p=0.804
24.5 mos 25.2 mos 24.3 mos
Overall Survival
C20 versus D75 - HR: 1.01, p=0.997; C25 versus D75 - HR: 0.98, p=0.757
Total Grade 3/4 AEs 41.2% 60.1% 46.0%
AE-related
25.2% 31.7% 33.9%
Most common Grade Febrile neutropenia (2.4%), Hematuria (3.5%), UTI Febrile neutropenia (12.0%), Hematuria (3.6%), UTI Febrile neutropenia (8.3%), Hematuria (0.3%), UTI
3/4 AEs* (3.3%) (2.0%) (0.8%)
Citation Oudard, J Clin Oncol, 2017
Clinical trial data that supported approvals in first-line mCRPC (vi)

PROpel TALAPRO-2 MAGNITUDE
Trial
NCT03732820 NCT03395197 NCT03748641
talazoparib +
Trial arms olaparib + abiraterone placebo + abiraterone placebo + talazoparib niraparib + abiraterone placebo + abiraterone
enzalutamide
ITT: 402 ITT: 403 212 211
Sample size 399 397
HRRm: n=399 (BRCA1/2mutant: 113) BRCA1/2mutant: 112)
Geography U.S., EU, JP, ROW U.S., EU, JP, CN, ROW U.S., EU, CN, ROW
Asymptomatic or mildly symptomatic mCRPC receiving
Indication mCRPC (BRCAm n=85) mCRPC, HRR+
ongoing androgen deprivation therapy
ITT: 24.8 mos ITT: 16.6 mos ITT: Not reached ITT: 21.9 mos HRR+: 16.7 mos HRR+: 13.7 mos
Radiographic BRCAm: not reached BRCAm: 8.4 mos HRR: not reached HRR: 13.8 mos BRCA1/2m: 16.6 mos BRCA1/2m: 10.9 mos
Progression Free
Survival ITT HR: 0.66, p<0.001 ITT HR: 0.63, p<0.0001 HRR+: 0.76, p=0.0280
BRCAm HR: 0.23 HRR HR: 0.45, p<0.0001 BRCA1/2m HR: 0.53, p=0.0014
ITT: 42.1 mos ITT: 34.7 mos HRR+: 29.3 mos HRR+: 32.2 mos
ITT: 36.4 mos ITT: Not reached
BRCAm: Not reached BRCAm: 23.0 mos BRCA1/2m: 30.4 mos BRCA1/2m: 28.6 mos
Overall Survival
ITT HR: 0.81, p=0.0544 HRR+ HR 1.01, p=0.9480
ITT: HR: 0.89, p=0.35
BRCAm HR: 0.29 BRCA1/2m HR: 0.79, p=0.5505
Total Grade 3/4 AEs 47.2% 38.4% 71.9% 40.6% 72.2% 49.3%
AE-related olaparib discontinuation: placebo discontinuation: talazoparib placebo discontinuation:
15.1% 5.7%
discontinuation rate 13.8% 7.8% discontinuation: 19.1% 12.2%
anemia (15%),venous anemia (3%), venous
anemia (47%), anemia (4%), anemia (30%) anemia (9%)
Most common Grade embolic and thrombotic embolic and thrombotic
neutropenia(18%), neutropenia(2%), hypertension (16%) hypertension (12%)
3/4 AEs* events (7%), hypertension events (2%), hypertension
leukopenia (6%) leukopenia (0%) thrombocytopenia (7%) fatigue (5%)
(4%) (3%)
Clarke, NEJM Evidence, 2022; Clarke, J Clin Onc, 2023, Agarwal, J Clin Oncol, 2023, LBA17; Agarwal, Lancet, 2023;
Citation Chi, Ann Oncol, 2023; FDA Press Release, Aug 11, 2023
LBA16 Pfizer Press Release, June 4, 2023
mCRPC: Treatment Jump to Table 43, Table 44 and Table 53
FIRST-LINE SYSTEMIC THERAPY: Enzalutamide and abiraterone are used in more than half of
both asymptomatic and symptomatic patients
First-Line Treatment Utilization, + Abiraterone plus prednisone and enzalutamide are the most commonly used regimens for first-line
mCRPC, U.S., 2023 (Table 43)a mCRPC, regardless of whether patients are asymptomatic or symptomatic. Enzalutamide is the preferred
single agent regimen with about 35-40% utilization.
100%
Other + Of mCRPC patients receiving abiraterone, 59% of patients receive generic abiraterone, with the remaining
16% 14%
90% patients receiving branded agents (Table 53)c
80%
7%
+ Docetaxel-based regimens, the standard first-line regimen prior to the approval of second-generation
8% radium Ra 223
14% dichloride hormone therapies, are still used in approximately 20-30% of patients.
70%
12%
+ The vast majority of patients continue to receive concurrent ADT with first-line therapy.
60% docetaxel,
15%
prednisone
50% 23% First-line treatment of mCRPC has remained stable over the past few years.
16% docetaxel
40%
Choice of regimen varies slightly globally, with a preference for abiraterone over enzalutamide in
30%
abiraterone, CN. However, in the U.S. enzalutamide is preferred, while in the E.U. and Japan enzalutamide
prednisone and abiraterone are used almost equally. Greater utilization of docetaxel is seen in China (~45%),
20% 38% 34% compared to the other regions (~15-40%).
10% enzalutamide
Utilization of ADT Concurrent with First-Line Therapy,
0% mCRPC, U.S., 2023 (Table 44)b
Asymptomatic Symptomatic 82% 18%
mCRPC mCRPC
Receive concurrent ADT Do not receive concurrent ADT
a) QP41.1 (n=94 asymptomatic, n=95 symptomatic): Of your metastatic Stage IV (M1) CRPC patients who receive initial systemic therapy for mCRPC diseases,
what percent receive the following regimens? b) QP41A (n=100): Of your patients who receive systemic therapy for the initial treatment of mCRPC, what percent
continue androgen deprivation therapy (ADT) concurrent with the regimens selected in the previous question? c) QP51B (n=67): With regard to your administration CancerMPact® Treatment Architecture U.S., Prostate Cancer 100
of abiraterone, what percentage of the time do you administer abiraterone generic, Yonsa brand or Zytiga brand? Note: “Other” category includes various therapies
used in <5% of patients each; Duration of therapy data is reported in the appendix.
Clinical trial data that supported approvals in relapsed mCRPC (i)

TROPIC COU-AA-301 AFFIRM PROSELICA
Trial
NCT00417079 NCT00638690 NCT00974311 NCT01308580
cabazitaxel 20 cabazitaxel 25
cabazitaxel, mitoxantrone, abiraterone,
Trial arms prednisone enzalutamide placebo mg/m2, mg/m2,
prednisone prednisone prednisone
prednisone prednisone
Sample size 378 377 797 398 800 399 598 602
Geography U.S., EU, ROW U.S., EU, ROW U.S., EU, ROW U.S., EU, ROW
Indication docetaxel pre-treated mCRPC docetaxel pre-treated mCRPC docetaxel pre-treated mCRPC docetaxel pre-treated mCRPC
≥ 50% decline: ≥ 50% decline: ≥ 50% decline: ≥ 50% decline: ≥ 50% decline: ≥ 50% decline: ≥ 50% decline:
PSA Response Rate ≥ 50% decline: 2%
39.2% 17.8% 29.5% 5.5% 54% 29.5% 42.9%
Median Radiographic 2.8 mos 1.4 mos 5.6 mos 3.6 mos 8.3 mos 2.9 mos mPFS: 2.9 mos mPFS: 3.5 mos
PFS HR 0.74, p < 0.0001 HR 0.66, p < 0.0001 HR 0.40, p < 0.001 NR
15.1 mos 12.7 mos 15.8 mos 11.2 mos 18.4 mos 13.6 mos 13.4 mos 14.5 mos
Overall Survival
HR 0.70, p < 0.0001 HR 0.74, p < 0.0001 HR 0.63, p < 0.001 HR 1.024
Total Grade 3/4 AEs Not reported Not reported Not reported Not reported 45% 53% 39.7% 54.5%
AE-related
18% 8% 13% 18% Not reported Not reported 16.4% 19.5%
Neutropenia Neutropenia
Neutropenia Neutropenia Fatigue (6%), Fatigue (7%),
Fatigue (9%), Fatigue (10%), (41.8%), (73.5%),
Most common Grade (82%), diarrhea (58%), diarrhea diarrhea (1%), diarrhea (<1%),
anemia (8%), anemia (8%), leukopenia leukopenia
3/4 AEs* (6%), febrile (<1%), febrile musculoskeletal musculoskeletal
back pain (7%) back pain (10%) (28.9%), anemia (59.5%), anemia
neutropenia (8%) neutropenia (1%) pain (1%) pain (<1%)
(9.9%) (17.3%)
Citation de Bono, Lancet, 2010 Fizazi, Lancet Oncol, 2012 Scher, N Engl J Med, 2012 Eisenberger, J Clin Oncol, 2017
Clinical trial data that supported approvals in relapsed mCRPC (ii)

ALSYMPCA
Trial
NCT00699751
Trial arms radium-223 placebo
Sample size 614 307
Geography U.S., EU, ROW
Indication mCRPC with skeletal metastases, docetaxel pre-treated or ineligible for first-course of docetaxel
Biomarker None
≥ 30% decline: 16% ≥ 30% decline: 6%
PSA Response Rate
p<0.001
Median Time to PSA 3.6 mos 3.4 mos

Progression HR 0.64, p < 0.001
Median Radiographic Not reported Not reported

PFS Not reported
14.9 mos 11.3 mos
Overall Survival
HR 0.70, p < 0.001
Total Grade 3/4 AEs 56% 62%
AE-related
16% 21%
Most common Grade Bone pain (22%), anemia (13%), Bone pain (26%), anemia (13%),
3/4 AEs* thrombocytopenia (7%) thrombocytopenia (2%)
Citation Parker, N Engl J Med, 2013; Hoskin, Lancet Oncol, 2014; Parker, Eur Urol, 2018
Clinical trial data that supported approvals in relapsed mCRPC (iii)

PROfound Study TRITON2
Trial
NCT02987543 NCT02952534
Trial arms olaparib enzalutamide or abiraterone olaparib enzalutamide or abiraterone rucaparib
Cohort A+B Cohort A+B
Cohort A Cohort A
Sample size (BRCA1, BRCA2, ATM, or (BRCA1, BRCA2, ATM, or 115
(BRCA1, BRCA2, or ATM): 162 (BRCA1, BRCA2, or ATM): 83
HRR pathway gene): 256 HRR pathway gene): 131
Geography U.S., EU, JP, CH, ROW U.S., EU, ROW
androgen antagonist and
Indication androgen antagonist pre-treated mCRPC
taxane pre-treated mCRPC
Biomarker HRRm BRCAm
≥ 50% decline: 43% ≥ 50% decline: 8% ≥ 50% decline: 30% ≥ 50% decline: 10% 54.8%
PSA Response Rate
NR NR ─
Median Radiographic 7.4 mos 3.6 mos 5.8 mos 3.5 mos 9.0 mos
PFS HR 0.34, p<0.0001 HR 0.49, p<0.0001 ─
19.1 mos 14.7 mos 17.3 mos 14.0 12-mo OS: 73%
Overall Survival HR 0.69, p=0.0175 HR 0.79, p=0.0515
─
HR 0.42 (95% CI, 0.19-0.91; adjusted to include crossover) HR 0.55 (95% CI, 0.29 to 1.06; adjusted to include crossover)
Total Grade 3/4 AEs Not reported Not reported 51% 38% 60.9%
AE-related
Not reported Not reported 18% 8% 7.8%
Anemia (21%), Decreased Anemia (5%), Decreased Anemia (25.2%),
Most common Grade
Not reported Not reported lymphocytes (23%), lymphocytes (13%), thrombocytopenia (9.6%),
3/4 AEs* thrombocytopenia (4%) thrombocytopenia (0%) fatigue (8.7%)
Citation de Bono, N Engl J Med, 2020; de Bono, Ann Oncol, 2020; Hussain M, N Engl J Med, 2020 Abida, J Clin Oncol, 2020
Clinical trial data that supported approvals in relapsed mCRPC (iv)

VISION
Trial
NCT03511664
Trial arms 177Lu-PSMA-617 BSC
Sample size 385 196
Geography U.S., EU
ARI and taxane
Indication
pretreated mCRPC
Biomarker PSMA
≥ 50% decline: 46.0% ≥ 50% decline: 7.1%
PSA Response Rate ≥ 80% decline: 33.0% ≥ 80% decline: 2.0%
NR
Median Radiographic 8.7 mos 3.4 mos

PFS HR 0.40, p<0.001
15.3 mos 11.3 mos
Overall Survival
HR 0.62, p<0.001
Total Grade 3/4 AEs 57.2% 38.0%
AE-related
1.9% NA
Anemia (12.9%), Anemia (4.9%),

Most common Grade
thrombocytopenia (7.9%), thrombocytopenia (1%),
3/4 AEs*
Lymphopenia (7.8%) Lymphopenia (0.5%)
Citation Sartor, NEJM, 2021
Clinical trial data that supports use of targeted agents in solid tumors
KEYNOTE-158 (NCT02628067)
MK-3475-016 GARNET
Trial** KEYNOTE-164 (NCT02460198) KEYNOTE-158 (NCT02628067)
(NCT01876511) KEYNOTE-051 (NCT02332668) (NCT02715284)
Trial arms pembrolizumab pembrolizumab pembrolizumab dostarlimab

Sample size 86 504 102 186
Geography U.S. U.S., EU, JP, ROW U.S., EU, JP, ROW U.S., EU
Biomarker dMMR solid tumors MSI-H/dMMR solid tumors TMB-H solid tumors dMMR solid tumors
advanced, R/R solid tumor
Stage IV (98%), 2L+ Stage IV M1 (91%), R/R Stage IV, R/R
Stages Enrolled MSI-H(+) or dMMR(+)
ECOG PS 0-1 ECOG PS 0-1 ECOG PS 0-1
ECOG PS0-1
CR: 10.3%
CR: 21% CR: 11.3%
Response Rate ORR: 33.3% 29%
ORR: 53% ORR: 43%
mDOR: 63.2 mo
mPFS: Not reached mPFS: 4.0 mo mPFS: 7.0 mo
Progression Free
1-yr PFS: 64% 1-yr PFS: 35.1% Not reported 1-yr estimated PFS: 45.6%
Survival
2-yr PFS: 53% 3-yr PFS: 25% 3-yr estimated PFS: 39.6%
mOS: Not reached mOS: 19.8 mo mOS: Not reached
Overall Survival 1-yr OS: 76% 1-yr OS: 58.6% Not reported 1-yr estimated OS: 69.6%
2-yr OS: 64% 2-yr OS: 39% 3-yr estimated OS: 55.0%
Total Grade 3/4 AEs* 20% 13% 10% TRAE: 15.7%
AE-related
Not reported 9.1% Not reported 2.6%
Most common Grade diarrhea / colitis (6%), pancreatitis (6%), severe skin toxicity (4%), pneumonitis ALT increased (5%), hypothyroidism
Colitis (2%)
3/4 AEs* fatigue (2%) (1%), colitis (1%) (5%), AST increased (3%)
Marabelle, J Clin Oncol, 2020; Maio, Ann Oncol, Oaknin, JAMA Oncol, 2020; André, Ann Oncol,
Citation Le, Science, 2017
2022; Merck Pooled Analysis, March 2023
Marabelle, Lancet Oncol, 2020
2022
have a stipulated primary endpoint per-protocol. Please refer to Appendix (Table A.1) for definitions of abbreviations.
*Shown are the top 3 Grade 3/4 adverse events reported for the experimental arm or arm with the highest efficacy. **Pan-tumor
approval. Data is not specific to prostate cancer unless otherwise noted
mCRPC: Treatment Jump to Table 45 and Table 46
SECOND-LINE SYSTEMIC THERAPY: Taxane usage is used in over one-third of patients, with
another quarter receiving second-generation ARIs
Second-Line Systemic Therapy Utilization, + Care in second line mCRPC becomes more fractured, as patients progress through multiple
mCRPC, U.S., 2023 (Table 45)a lines.
100% + Around 37% of patients will receive a taxane, with 23% of that being docetaxel with or
Other without a steroid.
90% 19%
olaparib + Abiraterone plus prednisone and enzalutamide are still used for about 25% of patients.
80%
6% + The PARP inhibitors olaparib and rucaparib capture about 9% share in second-line
radium Ra 223 dichloride
70% 7% mCRPC.
7% lutetium Lu 177 vipivotide

60% Usage of second-gen ARIs has decreased in second-line, likely due to their
tetraxetan
10% approval and usage in several earlier disease stages.
docetaxel, steroid
50%
10% In the 2L mCRPC setting, the majority of patients will receive either enzalutamide,
40% enzalutamide abiraterone, or a docetaxel-based regimen across all regions. Docetaxel-
13% containing regimens are utilized more heavily in China and Japan (~40-43%)
30% docetaxel compared to the U.S. and EU (~25-30%).
20% 14% cabazitaxel, steroid Utilization of ADT Concurrent with Second-Line Therapy,
10%
mCRPC, U.S., 2023 (Table 46)b
14% abiraterone, prednisone
0% 76% 24%
Second-Line
a) QP44.1 (n=98): Of your metastatic Stage IV (M1) CRPC patients who receive 2L systemic therapy, what percent receive the
following regimens? b) QP44A (n=100): Of your patients who receive systemic therapy for the treatment of 2L mCRPC, what
percent continue androgen deprivation therapy (ADT) concurrent with the regimens selected in the previous question? Note:
“Other” category includes various therapies used in <5% of patients each; Duration of therapy data is reported in the appendix.
mCRPC: Treatment Jump to Table 47
Most physicians switch their mCRPC patients to an agent with a different mechanism of action
for second-line therapy after progression on initial therapy for mCRPC
Second-Line Utilization of Systemic Therapy Based on First-Line Regimen Received,
mCRPC, U.S., 2023 (Table 47)*
FIRST-LINE SECOND-LINE
abiraterone, prednisone 23%
cabazitaxel, steroid 18% For patients who receive taxane-based first-
Taxane- enzalutamide 16% line therapy, abiraterone plus prednisone,
containing radium Ra 223 dichloride 7%
lutetium Lu 177 vipivotide tetraxetan 6% enzalutamide, and cabazitaxel plus
therapy pembrolizumab 5%
(24% asymp., docetaxel, steroid 4% prednisone are common choices as second-
33% symp.) docetaxel line therapies.
olaparib
Other 14%
abiraterone, prednisone 7%
cabazitaxel, steroid 9%
enzalutamide 29% For patients who received abiraterone plus
Abiraterone- radium Ra 223 dichloride 5% prednisone as first-line therapy, enzalutamide
based therapy lutetium Lu 177 vipivotide tetraxetan
(23% asymp.,
pembrolizumab 6% and docetaxel-containing regimens are
docetaxel, steroid 11%
16% symp.) docetaxel 16% preferred as second-line therapies.
olaparib 6%
Other 8%
abiraterone, prednisone 24% For patients who received enzalutamide as

cabazitaxel, steroid
Enzalutamide- enzalutamide 12%
first-line therapy, abiraterone plus
based therapy radium Ra 223 dichloride prednisone and docetaxel-containing
lutetium Lu 177 vipivotide tetraxetan 6%
(38% asymp, pembrolizumab regimens are preferred as second-line
34% symp.) docetaxel, steroid 13% therapies.
docetaxel 20%
olaparib 7%
Other 8%
*QP45.1 (n=67 taxane-based 1L, n=51 abiraterone-based 1L, n=69 enzalutamide-based 1L): What percent of metastatic Stage IV
(M1) CRPC patients receive the following regimens as second-line systemic therapy based on what they received in first-line? CancerMPact® Treatment Architecture U.S., Prostate Cancer 107
Note: “Other” category includes various therapies used in <5% of patients each.
mCRPC: Treatment Jump to Table 48, Table 49, and Table 52
THIRD- AND FOURTH-LINE SYSTEMIC THERAPY: Taxane-based regimens are preferred in

later lines, and nearly 25% of fourth-line patients are in a clinical trial
+ In the third-line and fourth-line settings, taxane therapy is still common for patients.
Third- and Fourth-Line Systemic
Therapy Utilization, mCRPC, U.S., 2023 + Pembrolizumab is used in a small proportion of third and fourth-line patients (7-8%); 47% of
(Table 48)a pembrolizumab-treated patients are treated based on MSI-H/dMMR status while 30% are treated
100% based on TMB-high in the relapsed setting (Table 52)c
Other
90% 15% 15% + Lutetium Lu 177 vipivotide tetraxetan is used in the third-line and fourth-line (12% each).
radium Ra 223 dichloride
80% 6% 7%
enzalutamide Regimen utilization has stayed consistent in 2023 compared to 2022.
5% 5%
70% 6%
abiraterone, prednisone
8%
7% U.S., Japan and EU5 physicians commonly prescribe cabazitaxel plus a steroid. In China
60%
pembrolizumab treatment varies with docetaxel-based therapies and second gen-ARIs. PARP inhibitors are
9%
50% 24% used in 3L and 4L across all regions (~5-13%). Pembrolizumab is used ~7% in U.S. patients.
Clinical Trial
12% Lutetium Lu 177 vipivotide tetraxetan has seen uptake in 3L and 4L in U.S. (~12%) and EU5
40%
lutetium Lu 177 vipivotide
(6-10%) patients following approvals in 2022.
7% tetraxetan
30% 12%
docetaxel, steroid
13%
20%
7% Utilization of ADT Concurrent with Third- and Fourth-Line Therapy,
cabazitaxel, steroid
mCRPC, U.S., 2023 (Table 49)b
10% 18% 17% docetaxel Third-Line 82% 18%
0% Fourth-Line 72% 28%
Third-Line Fourth-Line Percent (%) of Patients
a) QP48.1 / QP51.1: Of your metastatic Stage IV (M1) CRPC patients who receive third-line (n=82) / fourth-line (n=57) systemic therapy for CRPC disease, what
percent receive the following regimens? b) QP48A / QP51A: Of your patients who receive systemic therapy for the treatment of third-line (n=84) / fourth-line (n=58)
mCRPC, what percent continue androgen deprivation therapy (ADT) concurrent with the regimens selected in the previous question? c) QP51.5 (n=30): Of your CancerMPact® Treatment Architecture U.S., Prostate Cancer 108
patients who receive pembrolizumab for relapsed / refractory PROSTATE CANCER, what percent receive pembrolizumab based on MSI-H/dMMR or TMB status?
Note: “Other” category includes various therapies used in <5% of patients each; Duration of therapy data is reported in the appendix.
About 50% of patients who receive first-line therapy go on to receive second-line therapy, and
the rate of subsequent therapy decreases for later lines
Metastatic CRPC Patients Who Receive Later Lines of Systemic Therapy, U.S., 2023 (Table 50)*
1L Drug-Treated 1L Drug-Treated
Symptomatic mCRPC
1L
Asymptomatic mCRPC
100% 100%
Progressed and alive Progressed and Progressed and Progressed and alive Died before received
In long term response Died before received received 2L systemic In long term response –
but did not receive received 2L systemic
– no further therapy next line of therapy
next line of therapy therapy therapy
but did not receive next
line of therapy
next line of therapy no further therapy 2L
14.4% 18.4% 19.5% 47.7% 46.6% 18.4% 22.0% 13.0%
Progressed and alive Progressed and

In long term response Died before received
next line of therapy therapy 3L
17.7% 25.8% 20.7% 35.8%
Progressed and alive Progressed and

In long term response Died before received
next line of therapy therapy
4L
10.8% 33.9% 30.5% 24.8%
+ The declining proportion of patients who have progressive disease but do not receive a subsequent line of systemic therapy highlights continued unmet need in
mCRPC patients. This is most pronounced for fourth-line, where only one-quarter of patients receive treatment. More effective therapeutic options are thus
needed in later lines so that patients can receive further treatment.
+ Unmet need may continue to grow across lines of therapy as second-generation hormone agents continue to be used more in earlier-stage disease, which
may be filled by the entry of targeted agents such as PARP inhibitors.
*QP42 / QP46 / QP49: What are the treatment outcomes of your patients who receive first-line (asymptomatic n=95, symptomatic
n=96) / second-line (n=100) / third-line (n=77) systemic therapy for metastatic STAGE IV (M1) CRPC? Note: For results of fourth- CancerMPact® Treatment Architecture U.S., Prostate Cancer 109
line therapy and progression to fifth-line please see appendix.
Click for Table
Return to TableofofContents
Contents
Physicians report about 60% ORR in first-line asymptomatic patients with a PFS of over 1.5
years, but response rates and PFS decrease with each line of therapy
Results by Line of Therapy, mCRPC, U.S., 2023 (Table 51)

Response Ratesa Progression-Free Survivalb
First-Line Asymptomatic 23% 39% 19% 20.5
First-Line Symptomatic 18% 38% 20% 17.1
Second-Line 11% 31% 23% 12.5
Third-Line 8% 25% 21% 8.9
Fourth-Line 6% 20% 22% 6.3
Complete response rate Partial response rate Stable disease PFS (Months)
CR + PR = Objective Response Rate (ORR)
a) QP53 (1L asymptomatic n=96, 1L symptomatic n=97, 2L n=100, 3L n=84, 4L n=58): What are the responses of your metastatic
CRPC patients who received systemic therapy by line of systemic therapy? b) QP56 (1L asymptomatic n=96, 1L symptomatic
n=97, 2L n=100, 3L n=84, 4L n=58): Please estimate the average progression-free survival of your CRPC patients with Stage IV
(M1) disease for each line of systemic therapy.
Appendix
 Global trend comparisons
 Abbreviations used in this
report
 Survey respondent
demographics
 Full data tables
 References
 Cerner Enviza contact details
United States 2023 EU5 2023

Stage I Stage I
Stage II Stage II
Stage III Stage III
0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100%
leuprolide bicalutamide, leuprolide
Stage I enzalutamide, leuprolide Stage I leuprolide
bicalutamide, leuprolide goserelin
Stage II bicalutamide, leuprolide Stage II triptorelin
enzalutamide, leuprolide goserelin
Stage III enzalutamide, leuprolide Stage III goserelin
bicalutamide, leuprolide triptorelin
enzalutamide, leuprolide leuprolide
Stage IV (M0) leuprolide Stage IV (M0) enzalutamide, leuprolide
abiraterone, prednisone, leuprolide goserelin
U.S. and EU5. 2. All data are based on physician survey, as detailed in this report and other regional reports. 3. Top three CancerMPact® Treatment Architecture U.S., Prostate Cancer 112
regimens are listed unless top one or two regimens account for >70% of the utilization. Top regimen is bolded if it is at least twice
as frequent as the second in rank.
Japan 2023 China 2023

Stage I Stage I
Stage II Stage II
Stage III Stage III
0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100%

bicalutamide, goserelin goserelin
Stage I bicalutamide, leuprolide Stage I bicalutamide, leuprolide
leuprolide bicalutamide, goserelin
bicalutamide, goserelin bicalutamide, goserelin

Stage II bicalutamide, leuprolide Stage II bicalutamide, leuprolide
leuprolide goserelin

Stage III bicalutamide, leuprolide Stage III abiraterone, prednisone, goserelin
bicalutamide, degarelix abiraterone, prednisone, leuprolide

Stage IV (M0) bicalutamide, leuprolide Stage IV (M0) abiraterone, prednisone, goserelin
bicalutamide, degarelix abiraterone, prednisone, leuprolide
1. Based on CancerMPact® Patient Metrics, accessed in March 2023. Ranking is based on relative incidence of 48 tumors in China
and 29 tumors in Japan. 2. All data are based on physician survey, as detailed in this report and other regional reports. 3. Top CancerMPact® Treatment Architecture U.S., Prostate Cancer 113
three regimens are listed unless top one or two regimens account for >70% of the utilization. Top regimen is bolded if it is at least
twice as frequent as the second in rank.

0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100%
Stage I-III enzalutamide, leuprolide Stage I-III triptorelin
bicalutamide, leuprolide enzalutamide, leuprolide
enzalutamide, leuprolide leuprolide
Stage IV Stage IV
(M0) bicalutamide, leuprolide
(M0) abiraterone, prednisone, goserelin

Rank among all cancers1: 15
0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100%
bicalutamide, goserelin abiraterone, prednisone, goserelin

Stage I-III bicalutamide, leuprolide Stage I-III bicalutamide, goserelin
leuprolide abiraterone, prednisone, leuprolide
bicalutamide, goserelin abiraterone, prednisone, goserelin
Stage IV Stage IV
enzalutamide, goserelin bicalutamide, goserelin
(M0) bicalutamide, degarelix
(M0) abiraterone, prednisone, leuprolide

nmCRPC
nmCRPC
0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100%
0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100%
No therapy/Observation Active Surveillance

No therapy/Observation Active Surveillance Surgery RT
Surgery RT Systemic therapy ± Surgery Surgery, RT
Systemic therapy ± Surgery Surgery, RT Systemic therapy, RT Others
Systemic therapy, RT Others
enzalutamide apalutamide
nmCRPC nmCRPC
apalutamide darolutamide
darolutamide enzalutamide
1. Based on CancerMPact® Patient Metrics, accessed in February 2022. Ranking is based on relative incidence of 31 tumors in the

nmCRPC nmCRPC
0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100%

Systemic therapy ± Surgery Surgery, RT Systemic therapy ± Surgery Surgery, RT
darolutamide abiraterone, prednisone

nmCRPC nmCRPC
enzalutamide docetaxel, prednisone
abiraterone, prednisolone enzalutamide

mHSPC mHSPC
0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100%

Initial therapy enzalutamide, leuprolide apalutamide, leuprolide

Initial therapy
for mHSPC for mHSPC
apalutamide, leuprolide abiraterone, prednisone, leuprolide

abiraterone, prednisone, leuprolide goserelin, docetaxel
mHSPC apalutamide, leuprolide mHSPC enzalutamide, triptorelin

mHSPC mHSPC
0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100%
Initial therapy bicalutamide, goserelin Initial therapy bicalutamide, goserelin

bicalutamide, leuprolide abiraterone, prednisone, leuprolide
for mHSPC for mHSPC
enzalutamide, degarelix abiraterone, prednisone, goserelin

goserelin, docetaxel abiraterone, prednisone, goserelin
mHSPC abiraterone, prednisone, degarelix
mHSPC abiraterone, prednisone, leuprolide, docetaxel

Symtpomatic Symptomatic
0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100%
Top 3 Systemic Therapies for mCRPC3 Top 3 Systemic Therapies for mCRPC3
mCRPC enzalutamide enzalutamide mCRPC abiraterone, prednisone docetaxel, prednisone
abiraterone, prednisone abiraterone, prednisone enzalutamide abiraterone, prednisone
docetaxel docetaxel docetaxel, prednisone enzalutamide
Second-line for abiraterone, prednisone Second-line for docetaxel, steroid

mCRPC cabazitaxel, steroid mCRPC enzalutamide
docetaxel abiraterone, prednisone
docetaxel cabazitaxel, steroid

cabazitaxel, steroid enzalutamide
mCRPC mCRPC
lutetium Lu 177 vipivotide tetraxetan abiraterone, prednisone
Cancer Pact U.S. and EU5. 2. All data are based on physician survey, as detailed in this report and other regional reports. 3. Top CancerMPact® Treatment Architecture U.S., Prostate Cancer 120

Symptomatic Symptomatic
0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100%

Surgery, RT, Systemic therapy Others
Surgery, RT, Systemic therapy Others
Top 3 Systemic Therapies for mCRPC3
mCRPC mCRPC abiraterone, prednisone abiraterone, prednisone
docetaxel, prednisone docetaxel, prednisone
abiraterone, prednisolone abiraterone, prednisolone
Second-line for enzalutamide Second-line for abiraterone, prednisone

mCRPC abiraterone, prednisone mCRPC docetaxel
docetaxel enzalutamide
cabazitaxel, steroid abiraterone, prednisone

abiraterone, prednisolone docetaxel, steroid
mCRPC mCRPC
docetaxel docetaxel
Appendix
report
demographics
 References
Abbreviations used in this report (i)

Table A.1 Abbreviations Table A.1 Abbreviations
Abbreviation Expansion Abbreviation Expansion

3D three-dimensional EU5 Germany, France, Italy, Spain, United Kingdom
ADT androgen deprivation therapy FFS failure-free survival
AE adverse event GBq gigabecquerel
AJCC American Joint Committee on Cancer GnRH gonadotropin-releasing hormone
ARI Androgen receptor inhibitor HBOC hereditary breast and ovarian cancer
AR-V7 androgen receptor variant 7 HIFU high intensity focused ultrasound
BID twice daily HR hazard ratio
CR complete response HRD homologous recombination deficiency
CRPC castrate-resistant prostate cancer HRR homologous recombination repair
nmCRPC non-metastatic castrate-resistant prostate cancer HSPC hormone-sensitive prostate cancer
mCRPC metastatic castrate-resistant prostate cancer nmHSPC non-metastatic hormone-sensitive prostate cancer
CSCO Chinese Society of Clinical Oncology mHSPC metastatic hormone-sensitive prostate cancer
CTC circulating tumor cell IM intramuscular
DDR DNA damage repair IMRT intensity modulated radiation therapy
DFS disease-free survival ITT intention to treat
dMMR deficient mismatch repair IV intravenous
DRE digital rectal examination LHRH luteinizing hormone-releasing hormone
EAU European Association of Urology mAb monoclonal antibody
EBRT external beam radiation therapy mCi millicurie
EMA European Medicines Agency MHLW Ministry of Health, Labour and Welfare
ESMO European Society for Medical Oncology MHRA Medicines and Healthcare products Regulatory Agency
FDA Food and Drug Administration MOS months

Abbreviations used in this report (ii)

Table A.1 Abbreviations Table A.1 Abbreviations
Abbreviation Expansion Abbreviation Expansion

MSI-H microsatellite instability-high SBRT stereotactic body radiotherapy
NCCN National Comprehensive Cancer Network SC subcutaneous
NGS Next-generation sequencing SOC standard of care
NHA non-hormonal anti-androgens TID three times daily
NR not reported TMB tumor mutation burden
ORR overall response rate TNM Tumor, node, and metastasis
OS overall survival TRUS transrectal ultrasound
PBRT proton-beam radiation therapy TTP time to progression
PFS progression-free survival TURP transurethral resection of the prostate
PLND pelvic lymph node dissection
PO oral
PR partial response
PSA prostate-specific antigen
PSADT prostate-specific antigen doubling time
PSMA prostate-specific membrane antigen
QD once daily
QW every week
QxW every x weeks
RFS relapse-free survival
rPFS radiographic progression-free survival
RT radiotherapy

Appendix
report
demographics
 References
Survey Respondent Demographics
Table A.2 The Scope of the Survey, U.S., 2023
Survey fielded June, 2023

Number of physicians surveyed 112
Minimal number of years of practice after residency 5
Average number of years of practice after residency 15.9
Minimal number of prostate cancer patients treated by each physician monthly 30
Average number of prostate cancer patients treated by each physician monthly 78.9
Total number of prostate cancer patients treated by these physicians monthly 8,833
Table A.3 Physician Specialties, U.S., 2023 Table A.4 Physician Practice Settings, U.S., 2023
Specialties % of Physicians Practice Settings % of Physicians

Medical Oncology 17.9% Academic medical center (AMC) 26.8%
Hematology Oncology 10.7% Cancer center, affiliated with a hospital 14.3%
Medical Oncology/Hematology Oncology 19.6% Cancer center, independent 0.9%
Urology 51.8% Hospital, affiliated with a medical school 2.7%
Hospital, general 5.4%
Oncology group practice 14.3%
Private practice 35.7%

Survey Respondent Demographics
Table A.5 Physician Respondent Conference Attendance in the Past Two Years, U.S., 2023
Conference % of Physicians
American Society of Clinical Oncology (ASCO) 50.9%
European Society for Medical Oncology (ESMO) 16.1%
European CanCer Organisation (ECCO) 5.4%
ASCO, ESMO, or ECCO-associated Symposia 25.0%
National Comprehensive Cancer Network (NCCN) 25.0%
American Urology Association (AUA) 58.0%
European Association of Urology (EUA) 6.3%
American Society for Radiation Oncology (ASTRO) 7.1%
European Society for Therapeutic Radiology and Oncology (ESTRO) 3.6%
American Association for Cancer Research (AACR) 10.7%
Society of Urologic Oncology 1.8%
I did not attend a medical conference within the past two years 4.5%

Appendix
report
demographics
 References
Return to Discussion Slide
Table 1: Staging Distribution, Prostate Cancer, U.S., 2023
Table 1 Staging Distribution, Prostate Cancer, U.S., 2023
Stage Staging Distribution at Diagnosis Staging Distribution in Current Practice

Stage I 26.2% 23.6%
Stage II 20.1% 19.1%
Stage III 16.6% 16.3%
Stage IV (M0) 14.0% 14.8%
Stage IV (M1) 23.1% 26.1%
Source: Survey of 112 physicians who treat a total of 8,833 prostate cancer patients monthly, conducted in June 2023; 112 physicians completed
data for this question.
Cerner Enviza, 2023.

Table 2: Subtype Distribution, Prostate Cancer, U.S., 2023
Table 2 Subtype Distribution, Prostate Cancer, U.S., 2023
Subtypes % of Patients
Non-metastatic hormone sensitive (nmHSPC) 38.3%
Metastatic hormone sensitive (mHSPC) 19.1%
Non-metastatic castration resistant (nmCRPC) 18.3%
Metastatic castration resistant (mCRPC) 24.3%
Note: Please refer to Appendix (Table A.1) for definitions of abbreviations.
Source: Survey of 112 physicians who treat a total of 8,833 prostate cancer patients monthly,
conducted in June 2023; 112 physicians completed data for this question.

Table 3: Distribution of Patients by NCCN Risk Stratification, Prostate Cancer, U.S., 2023
Table 3 Distribution of Patients by NCCN Risk Stratification, Prostate Cancer, U.S., 2023
Newly Diagnosed Recurrent
% of physicians who classify based on risk 85.7% 75.0%
Risk Groups Newly Diagnosed Recurrent

Very low risk 14.9% 10.1%
Low risk 20.7% 13.1%
Intermediate risk 27.3% 22.5%
High risk 21.8% 29.4%
Very high risk 15.3% 24.9%
Source: Survey of 112 physicians who treat a total of 8,833 prostate cancer patients monthly, conducted in June
2023; 112 physicians completed data for use of classification by risk. 96 physicians completed data for newly
diagnosed patients by risk group and 82 physicians completed data for recurrent patients by risk group.

Table 4: Classification of Newly Diagnosed Intermediate Risk Patients based on NCCN,

Prostate Cancer, U.S., 2023
Table 4 Classification of Newly Diagnosed Intermediate Risk Patients based on NCCN, Prostate Cancer, U.S., 2023
Newly Diagnosed Recurrent
% of physicians who classify intermediate risk based on favorability 83.9% 85.1%
Classification Newly Diagnosed Recurrent

Favorable intermediate risk 50.6% 41.8%
Unfavorable intermediate risk 49.4% 58.2%
Source: Survey of 112 physicians who treat a total of 8,833 prostate cancer patients monthly, conducted in June 2023; 93 physicians completed
data for use of classification of risk by favorability for newly diagnosed and 74 physicians completed data for use of classification of risk by
favorability for recurrent. 78 physicians completed data for newly diagnosed patients by favorability and 63 physicians completed data for recurrent
patients by favorability.

Table 5: Treatment Decisions Based on NCCN Risk Stratification, Prostate Cancer, U.S., 2023
Table 5 Treatment Decisions Based on NCCN Risk Stratification, Prostate Cancer, U.S., 2023
Yes No
Newly-Diagnosed Local/Locally Advanced Patients 83.3% 16.7%
Stage I-IV(M0) HSPC Patients post first recurrence 70.7% 29.3%
Source: Survey of 112 physicians who treat a total of 8,833 prostate cancer patients monthly, conducted in June 2023; 96 physicians
completed data for Newly-Diagnosed Local/Locally Advanced and 82 physicians completed data for Stage I-IV9M0) .

Table 6: Biomarker Testing Rates, mHSPC, Prostate Cancer, U.S., 2023
Table 6 Biomarker Testing Rates, mHSPC, Prostate Cancer, U.S., 2023
AR-V7 BRCA HRR/HRD/DDR MSI/MMR TMB

% of patients tested at any point prior to first-line systemic therapy 26.2% 47.0% 41.6% 37.8% 35.3%
% of patients tested for the first time at any point after first-line systemic therapy 11.3% 17.0% 14.8% 13.6% 11.8%
% of patients NEVER tested for this biomarker 62.5% 36.0% 43.6% 48.6% 52.9%
Source: Survey of 112 physicians who treat a total of 8,833 prostate cancer patients monthly, conducted in June 2023; 107 physicians completed data for this question.

Table 7: Next-Generation Sequencing (NGS) Testing Patterns, HSPC, U.S., 2023
Table 7 Next-Generation Sequencing (NGS) Testing Patterns, HSPC, U.S., 2023
Line of Therapy % of Patients

Tested prior to start of first-line 36.0%
Tested prior to start of second-line 31.4%
Tested prior to start of third-line 25.5%
Source: Survey of 112 physicians who treat a total of 8,833 prostate cancer patients monthly, conducted in
June 2023; 107 physicians completed data for this question.

Table 8: Biomarker Testing Rates, mCRPC, U.S., 2023
Table 8 Biomarker Testing Rates, mCRPC, U.S., 2023
AR-V7 BRCA HRR/HRD/DDR MSI/MMR TMB PSMA

% of patients tested at any point prior to first-line systemic therapy 30.0% 50.2% 46.0% 38.6% 36.3% 42.7%
% of patients tested for the first time at any point after first-line systemic therapy 10.8% 17.6% 16.7% 14.6% 13.9% 15.6%
% of patients NEVER tested for this biomarker 59.2% 32.1% 37.2% 46.8% 49.8% 41.7%
Source: Survey of 112 physicians who treat a total of 8,833 prostate cancer patients monthly, conducted in June 2023; 106 physicians completed data for this question.

Table 9: Next-Generation Sequencing (NGS) Testing Patterns, mCRPC, U.S., 2023
Table 9 Next-Generation Sequencing (NGS) Testing Patterns, mCRPC, U.S., 2023
Line of Therapy % of Patients

Tested prior to start of first-line 46.8%
Tested prior to start of second-line 27.7%
Tested prior to start of third-line 24.4%

Table 10: Observation / Active Surveillance as Initial Management: Patients Eventually Treated
and Time to Active Therapy, by Stage and Hormone Sensitivity, Prostate Cancer, U.S., 2023
Table 10 Observation / Active Surveillance as Initial Management: Patients Eventually Treated and Time to Active Therapy, by Stage and Hormone Sensitivity,
Percent of Patients Under Percent of Patients Under “Active
Duration of “Observation / No Duration of “Active Surveillance”
Initial Management of HSPC “Observation / No therapy” Who Surveillance” Who Eventually
therapy” (Months) (Months)
Eventually Receive Treatment Receive Treatment
Stage I 35.4% n=33 30.5 n=33 35.4% n=78 31.5 n=78
Stage II 40.3% n=26 21.3 n=26 47.2% n=55 25.7 n=55
Stage III 44.4% n=16 13.8 n=16 58.4% n=24 16.2 n=24
Stage IV (M0) 34.6% n=27 13.3 n=27 42.9% n=16 16.5 n=16
Duration of “Observation / No Duration of “Active Surveillance”
Initial Management of nmCRPC “Observation / No therapy” Who Surveillance” Who Eventually
therapy” (Months) (Months)
Eventually Receive Treatment Receive Treatment
non-metastatic CRPC 41.2% n=24 12.5 n=21 49.3% n=21 13.2 n=21
% of newly-developed nmCRPC patients who remain untreated until they develop mCRPC 41.6% n=26
Source: Survey of 112 physicians who treat a total of 8,833 prostate cancer patients monthly, conducted in June 2023. Sample sizes are as noted in the table.

Table 11: Initial Treatment by Modality, nmHSPC, U.S., 2023
Table 11 Initial Treatment by Modality, nmHSPC, U.S., 2023
Modality Stage I Stage II Stage III Stage IV (M0)

Observation / No therapy 8.5% 4.3% 2.1% 3.3%
Active Surveillance 32.7% 12.6% 2.6% 2.4%
Surgery ONLY [cryosurgery, radical prostatectomy (RP)] 23.9% 29.7% 18.4% 3.2%
Radiotherapy (RT) ONLY [including External Beam
18.5% 24.2% 15.5% 5.7%
Radiotherapy (EBRT), Brachytherapy]
High Intensity Focused Ultrasound (HIFU) ONLY 2.3% 1.6% 1.4% 2.6%
Systemic therapy ONLY 4.5% 4.5% 9.0% 50.6%
Surgery, systemic therapy 2.1% 2.9% 6.8% 4.3%
Surgery, RT 1.5% 4.0% 9.7% 1.9%
RT, systemic therapy 2.3% 12.9% 26.9% 19.0%
Surgery, RT, systemic therapy 3.7% 3.4% 7.5% 6.8%
Orchiectomy ONLY 0.1% 0.0% 0.0% 0.1%
Note: Please refer to Appendix (Table A.1) for definitions of abbreviations. Systemic therapy includes hormone therapy, chemotherapy, immunotherapy,
radiopharmaceuticals, and other targeted therapies.
Source: Survey of 112 physicians who treat a total of 8,833 prostate cancer patients monthly, conducted in June 2023; 91 physicians completed data for Stage I, 98
physicians completed data for Stage II, 102 physicians completed data for Stage III and 103 physicians completed data for Stage IV (M0).

Table 12: Type of External Beam Radiotherapy, nmHSPC, U.S., 2023
Table 12 Type of External Beam Radiotherapy, nmHSPC, U.S., 2023
Type of Radiotherapy Stage I Stage II Stage III Stage IV (M0)

Proton beam radiation therapy 5.0% 8.0% 11.7% 11.2%
Stereotactic Body Radiation Therapy (SBRT) 19.0% 19.5% 16.8% 23.3%
Intensity Modulated Radiotherapy (IMRT) 62.9% 61.5% 62.2% 53.8%
Any other type of EBRT 13.0% 11.0% 9.4% 11.7%
Source: Survey of 112 physicians who treat a total of 8,833 prostate cancer patients monthly, conducted in June 2023; 71 physicians completed data for
Stage I, 90 physicians completed data for Stage II, 92 physicians completed data for Stage III and 69 physicians completed data for Stage IV (M0).

Table 13: Utilization and Number of Months of Systemic Therapy, Newly-Diagnosed nmHSPC,
U.S., 2023
Table 13 Utilization and Number of Months of Systemic Therapy, Newly-Diagnosed nmHSPC, U.S., 2023
Stage I Stage II Stage III Stage IV (M0)

Regimen Utilization No. of Months Utilization No. of Months Utilization No. of Months Utilization No. of Months
degarelix 4.2% 7.4 2.9% 11.1 3.8% 17.7 3.2% 14.7
goserelin 2.7% 7.2 2.0% 6.2 3.8% 15.3 2.3% 18.0
leuprolide 26.1% 15.4 37.9% 20.3 34.2% 22.2 16.8% 28.1
triptorelin 1.1% 12.7 0.6% 4.5 0.0% — 0.1% 24.0
relugolix 2.3% 6.0 4.9% 14.5 2.6% 22.2 1.6% 23.8
bicalutamide, goserelin 6.6% 7.8 0.7% 3.7 1.7% 4.8 0.7% 6.2
bicalutamide, leuprolide 14.7% 9.8 18.3% 20.6 13.4% 19.0 11.8% 24.2
bicalutamide, triptorelin 1.0% 5.0 0.7% 3.3 1.5% 4.5 1.3% 51.0
flutamide, goserelin 1.2% 3.5 1.3% 4.0 1.2% 3.3 0.8% 4.0
flutamide, leuprolide 1.3% 3.8 0.8% 4.3 0.0% — 0.0% —
flutamide, triptorelin 0.6% 3.3 2.3% 5.3 0.0% — 0.0% —
nilutamide, goserelin 1.2% 2.5 0.5% 2.5 0.0% — 0.3% 5.0
nilutamide, leuprolide 0.0% — 0.0% — 0.1% 4.0 0.0% —
nilutamide, triptorelin 0.0% — 0.0% 2.0 0.0% — 0.0% —
enzalutamide, goserelin 5.2% 5.2 2.6% 8.2 1.5% 12.0 1.1% 11.5
enzalutamide, leuprolide 15.1% 11.9 12.3% 15.4 19.2% 19.1 28.6% 24.3
enzalutamide, triptorelin 0.8% 13.3 2.1% 6.7 0.4% 12.0 0.9% 13.7
abiraterone, prednisone, goserelin 2.0% 4.8 1.2% 3.8 2.2% 13.4 3.3% 11.9
Source: Survey of 112 physicians who treat a total of 8,833 prostate cancer patients monthly, conducted in June 2023; 29 physicians completed data for Stage I, 51 physicians completed data for Stage II,
86 physicians completed data for Stage III and 98 physicians completed data for Stage IV (M0).
Continued on the next slide

Table 13 Continued: Utilization and Number of Months of Systemic Therapy, Newly-Diagnosed

nmHSPC, U.S., 2023
Table 13 Utilization and Number of Months of Systemic Therapy, Newly-Diagnosed nmHSPC, U.S., 2023 Continued
Stage I Stage II Stage III Stage IV (M0)

Regimen Utilization No. of Months Utilization No. of Months Utilization No. of Months Utilization No. of Months
abiraterone, prednisone, leuprolide 3.7% 7.1 2.1% 12.5 5.2% 16.9 12.7% 23.5
abiraterone, prednisone, triptorelin 0.8% 5.3 0.1% 2.0 0.4% 5.0 0.4% 4.3
goserelin, docetaxel 5.0% 3.8 0.1% 6.0 0.6% 3.0 0.4% 3.0
leuprolide, docetaxel 0.2% 5.0 2.8% 9.8 5.4% 8.6 8.0% 11.8
triptorelin, docetaxel 0.2% 4.0 0.1% 5.5 0.5% 3.7 0.3% 5.0
bicalutamide, goserelin, docetaxel 1.4% 3.0 0.6% 3.0 1.0% 3.8 0.9% 9.8
bicalutamide, leuprolide, docetaxel 0.1% 3.0 0.5% 3.5 0.7% 6.5 1.5% 10.9
bicalutamide, triptorelin, docetaxel 0.1% 4.0 0.1% 4.0 0.1% 3.0 0.5% 4.0
flutamide, goserelin, docetaxel 0.1% 4.0 0.6% 4.3 0.4% 3.0 0.4% 4.5
flutamide, leuprolide, docetaxel 1.0% 6.3 1.0% 6.0 0.0% — 0.0% —
flutamide, triptorelin, docetaxel 0.1% 3.0 0.1% 3.0 0.0% — 0.0% —
nilutamide, goserelin, docetaxel 0.6% 3.0 0.1% 3.0 0.0% — 0.2% 6.0
nilutamide, leuprolide, docetaxel 0.1% 3.0 0.4% 3.5 0.0% — 0.0% —
nilutamide, triptorelin, docetaxel 0.4% 3.0 0.1% 2.0 0.0% — 0.0% —
Investigational Drug (Clinical Trial) 0.0% — 0.3% — 0.2% — 1.6% —
darolutamide, leuprolide, docetaxel 0.0% — 0.0% — 0.0% — 0.1% 42.0
abiraterone, leuprolide, docetaxel 0.0% — 0.0% — 0.0% — 0.1% 36.0
apalutamide, leuprolide 0.0% — 0.0% — 0.0% — 0.1% 36.0
Source: Survey of 112 physicians who treat a total of 8,833 prostate cancer patients monthly, conducted in June 2023; 29 physicians completed data for Stage I, 51 physicians completed data for Stage II,
86 physicians completed data for Stage III and 98 physicians completed data for Stage IV (M0).

Table 14: Results of Initial Therapy by Stage, nmHSPC, U.S., 2023
Table 14 Results of Initial Therapy by Stage, nmHSPC, U.S., 2023
Response Rate Stage I Stage II Stage III Stage IV (M0)

Patients who do not respond to therapy (refractory) 6.6% 7.8% 9.8% 14.7%
Patients who respond but relapse within one year of therapy 9.0% 11.1% 17.3% 21.9%
Patients who respond but relapse between one and five years of therapy 18.4% 20.9% 27.4% 34.8%
Patients who respond but relapse between five and 10 years of therapy 15.8% 22.0% 20.1% 17.2%
Patients who respond and do not relapse within 10 years of therapy 50.2% 38.2% 25.4% 11.4%
Note: The data are presented as an overall average for first-line treatment, regardless of the modalities utilized.
Source: Survey of 112 physicians who treat a total of 8,833 prostate cancer patients monthly, conducted in June 2023; 90 physicians completed data for Stage I,
98 physicians completed data for Stage II, 102 physicians for Stage III, and 104 physicians for Stage IV (M0).

Table 15: Type of First Recurrence by Initial Diagnosed Stage, nmHSPC, U.S., 2023
Table 15 Type of First Recurrence by Initial Diagnosed Stage, nmHSPC, U.S., 2023
Recurrence Type Stage I Stage II Stage III Stage IV (M0)

Biochemical recurrence only (rising PSA and/or absolute PSA levels) but remain hormone sensitive 55.1% 42.2% 26.7% 13.5%
Biochemical recurrence only (rising PSA and/or absolute PSA levels) and become castrate-resistant (CRPC) 12.9% 16.1% 16.0% 15.2%
Confirmed radiographic diagnosis of local recurrence but remain hormone sensitive 13.3% 16.6% 19.6% 13.9%
Confirmed radiographic diagnosis of local recurrence and become CRPC 8.0% 9.8% 14.6% 21.2%
Metastatic recurrence but remain hormone sensitive 5.7% 9.5% 14.3% 16.7%
Metastatic recurrence and become CRPC 5.0% 5.8% 8.9% 19.6%
Note: Please refer to Appendix (Table A.1) for definitions of abbreviations. The data are presented as an overall average for first-line treatment, regardless of the modalities utilized.
Source: Survey of 112 physicians who treat a total of 8,833 prostate cancer patients monthly, conducted in June 2023; 78 physicians completed data for Stage I, 94 physicians completed
data for Stage II, 100 physicians for Stage III, and 102 physicians for Stage IV (M0).

Table 16: Extent of Diagnosed Radiographically-Confirmed Local Recurrence by Initial

Diagnosed Stage, Prostate Cancer, U.S., 2023
Table 16 Extent of Diagnosed Radiographically-Confirmed Local Recurrence by Initial Diagnosed Stage, Prostate Cancer, U.S., 2023
Stage I Stage II Stage III

Patients whose recurrent disease is equivalent to Stage I-III disease 48.6% 43.6% 39.5%
Patients whose recurrent disease is equivalent to Stage IV (M0) disease 51.4% 56.4% 60.5%
Note: Please refer to Appendix (Table A.1) for definitions of abbreviations. The data are presented as an overall average for first-line treatment, regardless of the
modalities utilized.
Source: Survey of 112 physicians who treat a total of 8,833 prostate cancer patients monthly, conducted in June 2023; 54 physicians completed data for Stage I, 68
physicians completed data for Stage II and 82 physicians for Stage III.

Table 17: Length of Time before Developing a Metastatic First Recurrence, HSPC, U.S., 2023
Table 17 Length of Time before Developing a Metastatic First Recurrence, HSPC, U.S., 2023
Time between newly diagnosed, non-metastatic disease and

24.1 19.7
development of metastatic disease at first confirmed recurrence (months)
completed data for Stages I-III and 63 physicians completed data for Stage IV (M0).

Table 18: Treatment by Modality and Prior Therapy, Newly-Recurrent HSPC, U.S., 2023
Table 18 Treatment by Modality and Prior Therapy, Newly-Recurrent HSPC, U.S., 2023
Post-Definitive Post-Systemic
Modality Post-Surgery
Radiotherapy Therapy Only
Observation / No therapy 6.2% 6.1% 4.0%
Active Surveillance 6.2% 6.7% 3.5%
Surgery only 10.0% 0.0% 3.1%
RT only 0.0% 16.2% 7.6%
HIFU only 2.6% 4.4% 3.5%
Systemic therapy only 49.5% 34.2% 56.0%
Surgery, systemic therapy 8.5% 0.0% 2.6%
Surgery, RT 3.1% 0.0% 3.7%
RT, systemic therapy 10.1% 32.0% 14.2%
Surgery, RT (including EBRT pre- and/or post-op), systemic therapy 3.7% 0.0% 1.5%
Orchiectomy only 0.1% 0.4% 0.1%
Note: Please refer to Appendix (Table A.1) for definitions of abbreviations. Systemic therapy includes hormone therapy, chemotherapy, immunotherapy,
radiopharmaceuticals, and other targeted therapies.
Post-Definitive Radiotherapy, 87 physicians completed data for Post-Surgery and 74 physicians completed data for Post-Systemic Therapy Only.

Table 19: Observation / Active Surveillance as Management of First Recurrence: Patients

Eventually Treated and Time to Active Therapy, Newly-Recurrent HSPC, U.S., 2023
Table 19 Observation / Active Surveillance as Management of First Recurrence: Patients Eventually Treated and Time to Active Therapy,
Newly-Recurrent HSPC, U.S., 2023
Duration of “Observation / No therapy” Duration of “Active Surveillance”
“Observation / No therapy” Who Surveillance” Who Eventually Receive
(Months) (Months)
Eventually Receive Treatment Treatment
Stages I-IV (M0) 41.3% 12.5 55.2% 18.2
Source: Survey of 112 physicians who treat a total of 8,833 prostate cancer patients monthly, conducted in June 2023; 29 physicians completed data for "Observation / No Therapy" and 31 physicians
completed data for "Active Surveillance."

Table 20: Utilization and Number of Months of Systemic Therapy by Stage, nmHSPC - First
Local Recurrence, U.S., 2023
Table 20 Utilization and Number of Months of Systemic Therapy by Stage, nmHSPC - First Local Recurrence, U.S., 2023

Utilization No. of Months Utilization No. of Months
degarelix 2.7% 17.5 1.7% 14.0
goserelin 1.7% 18.5 1.8% 28.0
leuprolide 24.7% 26.1 8.2% 21.2
relugolix 4.7% 22.0 2.7% 15.4
bicalutamide, goserelin 2.9% 11.5 1.3% 17.0
bicalutamide, leuprolide 11.6% 24.5 12.8% 19.7
bicalutamide, triptorelin 1.6% 17.0 1.8% 13.0
flutamide, goserelin 0.3% 12.0 0.4% 24.0
flutamide, leuprolide 0.4% 12.0 0.9% 14.0
nilutamide, goserelin 0.5% 18.0 0.0% —
enzalutamide, goserelin 0.3% 12.0 0.4% 24.0
enzalutamide, leuprolide 20.9% 21.0 29.0% 20.2
enzalutamide, triptorelin 1.1% 4.0 0.2% 4.0
Source: Survey of 112 physicians who treat a total of 8,833 prostate cancer patients monthly, conducted in June 2023; 91 physicians completed data for Stages I-
III and 65 physicians completed data for Stage IV (M0).

Table 20 Continued: Utilization and Number of Months of Systemic Therapy by Stage, nmHSPC
- First Local Recurrence, U.S., 2023
Table 20 Utilization and Number of Months of Systemic Therapy by Stage, nmHSPC - First Local Recurrence, U.S., 2023 Continued

abiraterone, prednisone, goserelin 1.5% 11.3 2.0% 22.0
abiraterone, prednisone, leuprolide 10.5% 20.0 20.6% 23.3
abiraterone, prednisone, triptorelin 0.2% 4.0 0.9% 26.0
goserelin, docetaxel 0.6% 6.3 0.7% 13.5
leuprolide, docetaxel 6.0% 15.2 5.9% 10.3
triptorelin, docetaxel 0.1% 3.0 0.3% 3.0
bicalutamide, goserelin, docetaxel 0.3% 3.5 0.3% 3.0
bicalutamide, leuprolide, docetaxel 2.0% 13.4 3.2% 19.5
bicalutamide, triptorelin, docetaxel 0.7% 6.0 1.1% 6.5
flutamide, goserelin, docetaxel 0.6% 2.5 0.0% —
flutamide, leuprolide, docetaxel 1.6% 8.2 0.3% 10.0
nilutamide, leuprolide, docetaxel 1.0% 8.0 0.0% —
Investigational Drug (Clinical Trial) 0.2% — 1.9% —
darolutamide, ADT 1.1% 20.0 1.5% 20.0
Source: Survey of 112 physicians who treat a total of 8,833 prostate cancer patients monthly, conducted in June 2023; 91 physicians completed data for Stages I-
III and 65 physicians completed data for Stage IV (M0).

Table 21: Results of Therapy by Stage at First Recurrence, nmHSPC, U.S., 2023
Table 21 Results of Therapy by Stage at First Recurrence, nmHSPC, U.S., 2023
Response Rate Stages I-III Stage IV (M0)

Patients who do not respond to therapy (refractory) 11.3% 16.6%
Patients who respond but relapse within one year of therapy 17.5% 23.6%
Patients who respond but relapse between one and five years of therapy 34.4% 32.8%
Patients who respond but relapse between five and 10 years of therapy 18.5% 16.3%
Patients who respond and do not relapse within 10 years of therapy 18.3% 10.6%
Source: Survey of 112 physicians who treat a total of 8,833 prostate cancer patients monthly, conducted in June 2023; 98 physicians completed data for Stages I-III and 85
physicians completed data for Stage IV (M0).

Table 22: Type of Second Recurrence by Stage, nmHSPC, U.S., 2023
Table 22 Type of Second Recurrence by Stage, nmHSPC, U.S., 2023
Treatment Stage at First Local Recurrence

Biochemical recurrence only (rising PSA and/or absolute PSA levels) but remain hormone sensitive 21.8% 11.4%
Biochemical recurrence only (rising PSA and/or absolute PSA levels) and become castrate-resistant (CRPC) 18.4% 14.6%
Confirmed radiographic diagnosis of local recurrence but remain hormone sensitive 17.7% 15.1%
Confirmed radiographic diagnosis of local recurrence and become CRPC 14.1% 13.5%
Metastatic recurrence but remain hormone sensitive 13.0% 18.5%
Metastatic recurrence and become CRPC 15.0% 26.9%
Source: Survey of 112 physicians who treat a total of 8,833 prostate cancer patients monthly, conducted in June 2023; 94 physicians completed data for Stages I-III,
and 83 physicians completed data for Stage IV (M0).

Table 23: Extent of Diagnosed Second Local Recurrence, Prostate Cancer, U.S., 2023
Table 23 Extent of Diagnosed Second Local Recurrence, Prostate Cancer, U.S., 2023
Stages I-III at First Recurrence

Patients whose second recurrent disease is equivalent to Stage I-III disease 40.9%
Patients whose second recurrent disease is equivalent to Stage IV (M0) disease 59.1%
Source: Survey of 112 physicians who treat a total of 8,833 prostate cancer patients monthly, conducted in June 2023; 74
physicians completed data for Stages I-III.

Table 24: Length of Time Before Developing a Metastatic Second Recurrence, Non-Metastatic
Table 24 Length of Time Before Developing a Metastatic Second Recurrence, Non-Metastatic Prostate Cancer, U.S., 2023
Treatment Stage at First Local Recurrence

Time between first-confirmed local recurrence and development of metastatic disease at the second-confirmed recurrence (months) 20.3 17.3
Source: Survey of 112 physicians who treat a total of 8,833 prostate cancer patients monthly, conducted in June 2023; 59 physicians completed data for Stages I-III and 59 physicians completed
data for Stage IV (M0).

Table 25: Treatment by Modality by Initial Diagnosed Stage, Second Recurrent HSPC, U.S.,
2023
Table 25 Treatment by Modality by Initial Diagnosed Stage, Second Recurrent HSPC, U.S., 2023
Modality Stages I-III Stage IV (M0)

Observation / No therapy 4.6% 3.9%
Active Surveillance 4.2% 3.2%
Surgery only 3.3% 4.5%
RT only 6.6% 6.7%
HIFU only 0.5% 1.9%
Systemic therapy only 54.0% 54.2%
Surgery, systemic therapy 5.6% 4.9%
Surgery, RT 2.1% 3.3%
RT, systemic therapy 15.4% 12.1%
Surgery, RT, systemic therapy 3.8% 5.1%
Orchiectomy only 0.0% 0.2%
Note: Please refer to Appendix (Table A.1) for definitions of abbreviations. Systemic therapy includes hormone therapy, chemotherapy,
immunotherapy, radiopharmaceuticals, and other targeted therapies.
completed data for Stage I-III, and 57 physicians for Stage IV (M0).

Table 26: Utilization and Number of Months of Systemic Therapy by Initial Diagnosed Stage,
nmHSPC - Second Local Recurrence, U.S., 2023
Table 26 Utilization and Number of Months of Systemic Therapy by Initial Diagnosed Stage, nmHSPC - Second Local
Recurrence, U.S., 2023
degarelix 2.4% 17.8 2.4% 10.0
goserelin 0.1% 18.0 0.0% —
leuprolide 11.2% 19.1 7.5% 17.9
triptorelin 0.2% 18.0 0.0% —
relugolix 2.5% 16.0 1.6% 11.3
bicalutamide, goserelin 2.0% 17.0 0.5% 12.0
bicalutamide, leuprolide 6.7% 20.4 6.9% 19.0
bicalutamide, triptorelin 0.0% — 0.9% 3.0
flutamide, leuprolide 2.0% 5.7 2.5% 12.7
nilutamide, goserelin 0.0% — 2.0% 12.0
nilutamide, leuprolide 0.1% 4.0 0.0% —
nilutamide, triptorelin 1.4% 6.0 2.0% 6.0
enzalutamide, goserelin 1.8% 7.5 0.7% 12.0
enzalutamide, leuprolide 31.3% 16.7 31.2% 18.3
enzalutamide, triptorelin 0.7% 14.0 0.8% 24.0
Stage I-III and 51 physicians completed data for Stage IV (M0).

Table 26 Continued: Utilization and Number of Months of Systemic Therapy by Initial

Diagnosed Stage, nmHSPC - Second Local Recurrence, U.S., 2023
Table 26 Utilization and Number of Months of Systemic Therapy by Initial Diagnosed Stage, nmHSPC - Second Local
Recurrence, U.S., 2023 Continued
abiraterone, prednisone, goserelin 2.0% 10.0 0.9% 3.5
abiraterone, prednisone, leuprolide 11.0% 14.9 7.7% 12.8
abiraterone, prednisone, triptorelin 2.5% 12.3 3.4% 11.8
goserelin, docetaxel 0.0% — 0.5% 12.0
leuprolide, docetaxel 10.3% 13.6 10.6% 12.9
triptorelin, docetaxel 0.0% — 0.0% —
bicalutamide, goserelin, docetaxel 0.9% 18.0 0.4% 12.0
bicalutamide, leuprolide, docetaxel 3.0% 10.5 5.1% 10.5
bicalutamide, triptorelin, docetaxel 0.9% 5.0 1.7% 12.7
flutamide, goserelin, docetaxel 0.9% 3.5 1.6% 19.0
flutamide, leuprolide, docetaxel 1.4% 10.7 2.5% 10.0
flutamide, triptorelin, docetaxel 0.9% 10.5 0.4% 3.0
nilutamide, goserelin, docetaxel 0.0% — 0.3% 4.0
nilutamide, leuprolide, docetaxel 0.6% 20.0 1.5% 9.0
nilutamide, triptorelin, docetaxel 0.0% — 0.3% 4.0
Stage I-III and 51 physicians completed data for Stage IV (M0).

Table 27: Initial Treatment by Modality, nmCRPC, U.S., 2023
Table 27 Initial Treatment by Modality, nmCRPC, U.S., 2023
Modality % of Patients
Observation / No therapy 5.1%
Active Surveillance 5.2%
Surgery only 3.1%
RT only 3.9%
HIFU only 1.1%
Systemic therapy only 58.7%
Surgery, systemic therapy 6.1%
Surgery, RT 2.9%
RT, systemic therapy 10.4%
Surgery, RT, systemic therapy 3.4%
Orchiectomy only 0.1%
Note: Please refer to Appendix (Table A.1) for definitions of abbreviations. Systemic therapy includes hormone
therapy, chemotherapy, immunotherapy, radiopharmaceuticals, and other targeted therapies.

Table 28: Utilization and Number of Months of Systemic Therapy, Initial Therapy for nmCRPC,
U.S., 2023
Table 27 Utilization and Number of Months of Systemic Therapy, Initial Therapy for nmCRPC, U.S., 2023
Regimen Utilization No. of Months

abiraterone, prednisone 18.3% 16.7
apalutamide 11.1% 21.1
bicalutamide 4.3% 12.0
corticosteroid (hydrocortisone, prednisone, dexamethasone) ONLY 1.4% 6.8
darolutamide 15.3% 20.9
diethylstilbestrol (DES) or other estrogen 0.9% 9.7
enzalutamide 38.8% 22.0
flutamide 1.4% 16.5
ketoconazole 0.1% 6.0
ketoconazole, hydrocortisone 0.8% 8.8
nilutamide 0.6% 24.0
docetaxel 2.9% 9.9
docetaxel, prednisone 2.6% 7.1
Investigational Drug (Clinical Trial) 1.6% —
physicians completed data for this question.

Table 29: Utilization of Androgen Deprivation Therapy Concurrent with Initial Therapy,
nmCRPC, U.S., 2023
Table 29 Utilization of Androgen Deprivation Therapy Concurrent with Initial Therapy, nmCRPC, U.S., 2023
% of Patients
Receive androgen deprivation therapy (ADT) concurrent with non-ADT regimens 79.9%
Do not receive androgen deprivation therapy (ADT) concurrent with non-ADT regimens 20.1%
physicians completed data for this question.

Table 30: Results of Initial Therapy, nmCRPC, U.S., 2023
Table 30 Results of Initial Therapy, nmCRPC, U.S., 2023
Response Rate % of Patients

Patients who do not respond to therapy (refractory) 12.0%
Patients who respond but relapse within one year of therapy for first recurrence 24.7%
Patients who respond but relapse between one and five years of therapy for first recurrence 42.3%
Patients who do not relapse within five years of therapy for first recurrence 21.1%
completed data for this question.

Table 31: Location of Recurrence, nmCRPC, U.S., 2023
Table 31 Location of Recurrence, nmCRPC, U.S., 2023
% Local recurrence % Metastatic recurrence
nmCRPC patients 35.7% 64.3%

Source: Survey of 112 physicians who treat a total of 8,833 prostate cancer patients monthly, conducted in June 2023;
96 physicians completed data for this question.

Table 32: Length of Time Before Developing a Metastatic Recurrence, CRPC, U.S., 2023
Table 32 Length of Time Before Developing a Metastatic Recurrence, CRPC, U.S., 2023
Time between newly diagnosed nmCRPC disease and development of metastatic Stage IV (M1) disease (months) 18.6
this question.

Table 33: Sources of Metastatic Patients: mHSPC, Metastatic Prostate Cancer, U.S., 2023
Table 33 Sources of Metastatic Patients: mHSPC, Metastatic Prostate Cancer, U.S., 2023
% of Patients
Newly diagnosed metastatic patients 40.8%
mHSPC patients who recur from non-metastatic disease 30.4%
mCRPC patients who recur from non-metastatic disease 28.8%
this question.

Table 34: Initial Treatment by Modality, mHSPC, U.S., 2023
Table 34 Initial Treatment by Modality, mHSPC, U.S., 2023
Modality % of Patients
Observation / No therapy 3.1%
Active Surveillance 2.1%
Surgery only 1.8%
RT only 1.7%
HIFU only 0.8%
Systemic therapy only 68.3%
Surgery, systemic therapy 4.9%
Surgery, RT 0.9%
RT, systemic therapy 11.6%
Surgery, RT, systemic therapy 4.9%
Orchiectomy only 0.1%
Source: Survey of 112 physicians who treat a total of 8,833 prostate cancer patients
monthly, conducted in June 2023; 109 physicians completed data for recurrent metastatic
patients.

Table 35: Utilization and Number of Months of Systemic Therapy, Initial Therapy for mHSPC,
U.S., 2023
Table 35 Utilization and Number of Months of Systemic Therapy,
Initial Therapy for mHSPC, U.S., 2023
Utilization No. of Months

degarelix 1.0% 21.2
goserelin 1.2% 19.5
leuprolide 6.1% 18.2
relugolix 1.8% 15.2
bicalutamide, goserelin 1.1% 5.5
bicalutamide, leuprolide 8.1% 27.5
bicalutamide, triptorelin 1.0% 24.0
flutamide, leuprolide 0.7% 8.5
nilutamide, leuprolide 0.1% 4.0
apalutamide, degarelix 0.7% 24.0
apalutamide, goserelin 0.3% 20.0
apalutamide, leuprolide 8.2% 20.5
apalutamide, triptorelin 0.6% 20.0
enzalutamide, degarelix 2.2% 24.8
enzalutamide, goserelin 1.0% 12.0
enzalutamide, leuprolide 25.4% 22.7
abiraterone, prednisone, degarelix 1.1% 27.2
abiraterone, prednisone, goserelin 0.9% 11.3
monthly, conducted in June 2023; 105 physicians completed data for recurrent
metastatic disease.

Table 35 Continued: Utilization and Number of Months of Systemic Therapy, Initial Therapy for
mHSPC, U.S., 2023
Initial Therapy for mHSPC, U.S., 2023 Continued
Utilization No. of Months

abiraterone, prednisone, leuprolide 12.9% 22.2
abiraterone, prednisone, triptorelin 0.2% 4.0
goserelin, docetaxel 1.5% 6.3
leuprolide, docetaxel 5.5% 10.6
triptorelin, docetaxel 0.8% 3.5
abiraterone, prednisone, goserelin, docetaxel 3.2% 7.7
abiraterone, prednisone, leuprolide, docetaxel 4.2% 15.4
bicalutamide, goserelin, docetaxel 0.3% 4.5
bicalutamide, leuprolide, docetaxel 1.1% 11.3
bicalutamide, triptorelin, docetaxel 0.6% 8.5
darolutamide, goserelin, docetaxel 0.6% 18.7
darolutamide, leuprolide, docetaxel 3.8% 16.4
darolutamide, triptorelin, docetaxel 0.1% 36.0
flutamide, goserelin, docetaxel 0.2% 20.0
flutamide, leuprolide, docetaxel 0.8% 12.8
darolutamide, ADT, docetaxel 0.3% 12.0
darolutamide, ADT 0.3% 11.0
darolutamide, relugolix 0.2% 18.0
conducted in June 2023; 105 physicians completed data for recurrent metastatic disease.

Table 36: Utilization and Number of Months of Systemic Therapy, Second-Line Therapy for
mHSPC, U.S., 2023
Second-Line Therapy for mHSPC, U.S., 2023

degarelix 0.4% 7.0
leuprolide 1.3% 11.9
triptorelin 0.3% 5.0
relugolix 0.9% 13.3
bicalutamide, goserelin 1.1% 18.0
bicalutamide, leuprolide 2.2% 8.8
bicalutamide, triptorelin 1.6% 7.3
flutamide, triptorelin 0.3% 5.0
nilutamide, leuprolide 0.2% 4.0
apalutamide, degarelix 2.8% 18.8
apalutamide, leuprolide 8.7% 16.7
apalutamide, triptorelin 0.2% 24.0
enzalutamide, degarelix 1.1% 26.0
enzalutamide, goserelin 2.1% 10.5
enzalutamide, leuprolide 20.2% 18.1
enzalutamide, triptorelin 1.5% 24.0
abiraterone, prednisone, degarelix 2.2% 19.0
abiraterone, prednisone, goserelin 2.0% 13.0
abiraterone, prednisone, leuprolide 13.2% 17.9
abiraterone, prednisone, triptorelin 1.5% 15.0
monthly, conducted in June 2023; 94 physicians completed data for this question.

Table 36 Continued: Utilization and Number of Months of Systemic Therapy, Second-Line

Therapy for mHSPC, U.S., 2023
Second-Line Therapy for mHSPC, U.S., 2023 Continued

goserelin, docetaxel 3.4% 7.3
leuprolide, docetaxel 8.1% 9.0
triptorelin, docetaxel 0.7% 3.5
abiraterone, prednisone, goserelin, docetaxel 0.8% 4.0
abiraterone, prednisone, leuprolide, docetaxel 5.1% 10.7
abiraterone, prednisone, triptorelin, docetaxel 0.4% 6.7
bicalutamide, leuprolide, docetaxel 2.2% 10.5
bicalutamide, triptorelin, docetaxel 0.3% 12.0
darolutamide, goserelin, docetaxel 2.4% 7.6
darolutamide, leuprolide, docetaxel 4.9% 12.5
flutamide, leuprolide, docetaxel 0.4% 4.0
flutamide, triptorelin, docetaxel 0.2% 18.0
nilutamide, goserelin, docetaxel 0.1% 5.0
nilutamide, leuprolide, docetaxel 0.3% 6.0
nilutamide, triptorelin, docetaxel 0.4% 5.0
sipuleucel-T 1.7% 3.7
radium Ra 223 dichloride 0.1% 2.0
olaparib 0.2% 12.0
lutetium Lu 177 vipivotide tetraxetan 1.1% 6.0

Table 37: mHSPC Patients Who Receive Later Lines of Systemic Therapy, U.S., 2023
Table 37 mHSPC Patients Who Receive Later Lines of Systemic Therapy, U.S., 2023
Response Rate First- to Second-Line Second- to Third-Line

Patients who achieved a long-term response and never receive the next line of systemic therapy 17.5% 12.5%
Patients who did not achieve a long-term response and died without receiving the next line of systemic therapy 13.4% 17.6%
Patients whose disease progressed and who remained hormone sensitive and survived, but did not receive the next line of systemic therapy 14.6% 13.2%
Patients whose disease progressed, who remained hormone sensitive, and who received the next line systemic therapy 20.6% 15.1%
Patients whose disease progressed and who became CRPC 34.0% 41.6%
Source: Survey of 112 physicians who treat a total of 8,833 prostate cancer patients monthly, conducted in June 2023; 105 physicians completed data for first-line recurrent metastatic disease and 95
physicians completed data for second-line metastatic disease.

Table 38: Time to Castration-Resistance in Patients with Metastatic Disease, Prostate Cancer,
U.S., 2023
Table 38 Time to Castration-Resistance in Patients with Metastatic Disease, Prostate Cancer, U.S., 2023
Recurrent HSPC Metastatic Disease

Time between initial treatment for mHSPC and becoming mCRPC (months) 17.3
recurrent metastatic disease.

Table 39: Results by Line of Therapy, mHSPC, U.S., 2023
Table 39 Results by Line of Therapy, mHSPC, U.S., 2023
Line of Therapy Complete Response Rate (%) Partial Response Rate (%) Stable Disease Rate (%) Progression-Free Survival (months)
Initial treatment for mHSPC 21.9% 34.7% 20.4% 21.6
Treatment for recurrent mHSPC 14.1% 33.0% 18.1% 12.6
Source: Survey of 112 physicians who treat a total of 8,833 prostate cancer patients monthly, conducted in June 2023; 105 physicians completed data for initial treatment and 95 physicians completed data
for second-line treatment.

Table 40: Administration of Androgen Receptor Inhibitor Prior to mCRPC Status, U.S., 2023
Table 40 Administration of Androgen Receptor Inhibitor Prior to mCRPC Status,

U.S., 2023
% of Patients
Receive ARI prior to mCRPC status 56.8%

Table 41: Symptomology Among mCRPC Patients, U.S., 2023
Table 41 Symptomology Among mCRPC Patients, U.S., 2023
Patients who first present as mCRPC

Asymptomatic mCRPC 49.9%
Symptomatic mCRPC 50.1%

Table 42: First-Line Treatment by Modality, mCRPC, U.S., 2023
Table 42 First-Line Treatment by Modality, mCRPC, U.S., 2023
Modality Asymptomatic Symptomatic

Observation / No therapy 4.8% 3.9%
Active Surveillance 2.7% 2.0%
Surgery only 1.8% 2.2%
RT only 2.4% 2.7%
HIFU only 0.7% 0.5%
Systemic therapy only 66.1% 63.4%
Surgery, systemic therapy 7.0% 6.5%
Surgery, RT 0.9% 0.8%
RT, systemic therapy 9.7% 13.1%
Surgery, RT, systemic therapy 3.9% 4.9%
Orchiectomy only 0.0% 0.1%
Note: Please refer to Appendix (Table A.1) for definitions of abbreviations. Systemic therapy includes hormone therapy,
chemotherapy, immunotherapy, radiopharmaceuticals, and other targeted therapies.
completed data for asymptomatic patients and 105 physicians completed data for symptomatic patients.

Table 43: Utilization and Number of Months of Systemic Therapy, First-Line mCRPC, U.S., 2023
Table 43 Utilization and Number of Months of Systemic Therapy, First-Line mCRPC, U.S., 2023
Asymptomatic Symptomatic
Regimen Utilization No. of Months Utilization No. of Months

abiraterone, prednisone 22.9% 16.1 16.4% 15.4
cabazitaxel, prednisone 1.9% 8.7 2.9% 9.2
docetaxel 12.4% 12.4 15.1% 11.9
docetaxel, prednisone 7.9% 9.0 13.8% 8.8
docetaxel, estramustine 1.4% 4.8 1.5% 5.8
enzalutamide 37.9% 17.2 33.9% 15.6
olaparib 3.7% 13.8 2.3% 16.4
mitoxantrone, prednisone 0.9% 7.6 1.7% 7.8
radium Ra 223 dichloride 3.0% 8.1 6.6% 6.9
sipuleucel-T 4.4% — 1.1% —
relugolix 0.7% 15.0 0.3% 24.0
completed data for asymptomatic disease and 95 physicians completed data for symptomatic disease.

Table 44: Utilization of Androgen Deprivation Therapy Concurrent with First-Line Therapy,
mCRPC, U.S., 2023
Table 44 Utilization of Androgen Deprivation Therapy Concurrent with First-Line Therapy,

mCRPC, U.S., 2023
% of Patients
2023; 100 physicians completed data for this question.

Table 45: Utilization and Number of Months of Systemic Therapy, Second-Line mCRPC, U.S.,
2023
Table 45 Utilization and Number of Months of Systemic Therapy, Second-Line mCRPC, U.S., 2023

abiraterone, prednisone 13.8% 12.8
cabazitaxel, steroid 13.7% 7.6
docetaxel 13.0% 10.1
docetaxel, steroid 9.6% 7.3
docetaxel, estramustine 0.8% 8.7
dostarlimab 2.9% 8.0
enzalutamide 10.5% 15.7
lutetium Lu 177 vipivotide tetraxetan 7.1% 8.1
mitoxantrone, steroid 0.7% 5.0
pembrolizumab 4.3% 9.0
radium Ra 223 dichloride 6.9% 6.9
olaparib 6.5% 12.7
rucaparib 2.0% 10.6
sipuleucel-T 3.8% —
abiraterone, enzalutamide, cabazitaxel 0.4% 6.0
this question.

Table 46: Utilization of Androgen Deprivation Therapy Concurrent with Second-Line Therapy,
mCRPC, U.S., 2023
Table 46 Utilization of Androgen Deprivation Therapy Concurrent with Second-Line Therapy,

mCRPC, U.S., 2023
% of Patients
2023; 100 physicians completed data for this question.

Table 47: Second-Line Utilization of Systemic Therapy Based on First-Line Regimen Received,
mCRPC, U.S., 2023
Table 47 Second-Line Utilization of Systemic Therapy Based on First-Line Regimen Received, mCRPC, U.S., 2023
First-Line Regimen: taxane-based therapy abiraterone-based therapy enzalutamide-based therapy

Second-Line Regimen Utilization Utilization Utilization
abiraterone, prednisone 22.8% 7.5% 24.2%
cabazitaxel, steroid 18.1% 9.4% 3.6%
docetaxel 4.0% 15.5% 19.7%
docetaxel, steroid 4.5% 11.5% 12.7%
docetaxel, estramustine 3.6% 0.0% 0.6%
dostarlimab 2.9% 0.4% 1.7%
enzalutamide 15.6% 29.4% 11.7%
lutetium Lu 177 vipivotide tetraxetan 6.0% 2.5% 5.8%
mitoxantrone, steroid 1.1% 0.0% 0.3%
pembrolizumab 4.7% 5.8% 4.1%
radium Ra 223 dichloride 6.6% 4.7% 3.3%
olaparib 3.5% 5.5% 6.6%
rucaparib 1.3% 3.2% 3.1%
sipuleucel-T 1.1% 1.5% 1.4%
Investigational Drug (Clinical Trial) 4.0% 3.2% 1.3%
cabazitaxel 0.2% 0.0% 0.0%
taxane-based therapy, 51 physicians completed data for abiraterone-based therapy and 69 physicians completed data for enzalutamide-based therapy.

Table 48: Utilization and Number of Months of Systemic Therapy, Third- and Fourth-Line
mCRPC, U.S., 2023
Table 48 Utilization and Number of Months of Systemic Therapy, Third- and Fourth-Line mCRPC, U.S., 2023
Third-Line Fourth-Line
Regimen Utilization No. of Months Utilization No. of Months
abiraterone, prednisone 6.3% 9.7 2.3% 8.3
cabazitaxel, steroid 13.4% 8.0 16.6% 9.3
docetaxel 18.3% 9.0 2.5% 6.3
docetaxel, steroid 6.8% 7.6 7.0% 6.2
docetaxel, estramustine 3.3% 7.0 3.0% 6.3
dostarlimab 1.0% 5.8 1.4% 9.0
enzalutamide 5.4% 13.5 4.8% 9.0
lutetium Lu 177 vipivotide tetraxetan 12.4% 7.1 12.4% 7.5
mitoxantrone, steroid 1.2% 7.8 2.5% 4.5
pembrolizumab 6.5% 8.4 8.0% 6.0
radium Ra 223 dichloride 6.2% 6.8 7.3% 5.6
olaparib 3.5% 11.2 2.5% 7.4
rucaparib 2.0% 9.9 2.8% 6.0
sipuleucel-T 3.4% — 2.9% —
cabazitaxel 1.1% 5.0 0.0% —
cyclophosphamide 0.0% — 0.4% 3.0
completed data for third-line, 57 physicians completed data for fourth-line.

Table 49: Utilization of Androgen Deprivation Therapy Concurrent with Third- and Fourth-Line
Therapy, mCRPC, U.S., 2023
Table 49 Utilization of Androgen Deprivation Therapy Concurrent with Third- and Fourth-Line Therapy, mCRPC, U.S., 2023
Third-Line Fourth-Line
Receive androgen deprivation therapy (ADT) concurrent with non-ADT regimens 81.8% 71.6%
Do not receive androgen deprivation therapy (ADT) concurrent with non-ADT regimens 18.3% 28.4%
Source: Survey of 112 physicians who treat a total of 8,833 prostate cancer patients monthly, conducted in June 2023; 84 physicians completed data for third-line and 58
physicians completed data for fourth-line.

Table 50: mCRPC Patients Who Receive Later Lines of Systemic Therapy, U.S., 2023
Table 50 mCRPC Patients Who Receive Later Lines of Systemic Therapy, U.S., 2023
First- to Second-line Second-Line to Third-Line to Fourth-Line to

Asymptomatic Symptomatic Third-Line Fourth-Line Fifth-Line
Patients who achieved a long-term response and never receive the next line of systemic therapy 14.4% 13.0% 17.7% 10.8% 13.1%
Patients who did not achieve a long-term response and died without receiving the next line of systemic therapy 18.4% 22.0% 25.8% 33.9% 37.7%
Patients whose disease progressed and who are alive but did not receive the next line of systemic therapy 19.5% 18.4% 20.7% 30.5% 32.9%
Patients whose disease progressed and who received the next line of systemic therapy 47.7% 46.6% 35.8% 24.8% 16.3%
Source: Survey of 112 physicians who treat a total of 8,833 prostate cancer patients monthly, conducted in June 2023; 95 physicians completed data for progression to second-line of asymptomatic
patients, 96 physicians completed data for progression to second-line of symptomatic patients, 100 physicians completed data for progression to third-line, 77 physicians completed data for progression
to fourth-line and 46 physicians completed data for progression to fifth-line.

Table 51: Results by Line of Therapy, mCRPC, U.S., 2023
Table 51 Results by Line of Therapy, mCRPC, U.S., 2023
Line of Therapy Complete Response Rate (%) Partial Response Rate (%) Stable Disease Rate (%) Progression-Free Survival (months)
First-line asymptomatic CRPC 22.9% 39.4% 19.1% 20.5
First-line symptomatic CRPC 17.6% 37.5% 20.4% 17.1
Second-line 11.5% 30.7% 23.2% 12.5
Third-line 7.6% 25.2% 21.0% 8.9
Fourth-line 6.3% 19.7% 22.3% 6.3
Source: Survey of 112 physicians who treat a total of 8,833 prostate cancer patients monthly, conducted in June 2023; 96 physicians completed data for first-line asymptomatic CRPC, 97 physicians
completed data for first-line symptomatic CRPC, 100 physicians completed data for second-line, 84 physicians completed data for third-line, and 58 physicians completed data for fourth-line.

Table 52: Pembrolizumab Utilization based on MSI/dMMR or TMB-High Status, Prostate Cancer,
U.S., 2023
Table 52 Pembrolizumab Utilization based on MSI/dMMR or TMB-High Status,

Biomarker % of Patients
MSI-H/dMMR 46.8%
TMB-High 29.9%

Table 53: Generic vs Branded Administration of Abiraterone, Prostate Cancer, U.S., 2023
Table 53 Generic vs Branded Administration of Abiraterone, Prostate Cancer, U.S., 2023
nmHSPC nmCRPC mHSPC mCRPC

abiraterone generic 58.4% 54.5% 60.2% 58.6%
Zytiga brand 31.4% 34.1% 29.8% 34.8%
Yonsa brand 10.2% 11.5% 10.0% 6.7%
Source: Survey of 112 physicians who treat a total of 8,833 prostate cancer patients monthly, conducted in June 2023; 58 physicians completed data for Non-metastatic hormone-
sensitive, 33 physicians completed data for Non-metastatic castration-resistant, 63 physicians completed data for Metastatic hormone-sensitive and 67 physicians completed data for
Metastatic castration-resistant.

Appendix
report
demographics
 References
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21;4(6)

Appendix
report
demographics
 References
Thank you to all Treatment Architecture contributors!
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CancerMPact® Treatment Architecture

Prostate Cancer, U.S.

Published September 2023

Definitions and Standard Abbreviations of Systemic Therapies 4 Role of Observation 35

CancerMPact® Treatment Architecture U.S., Prostate Cancer 2

CancerMPact® Treatment Architecture U.S., Prostate Cancer 3

Definition of hormone therapies / androgen pathway disruptors used in this report

Abbreviation Specific Agents Mechanism of action

LHRH agonists: leuprolide, goserelin, triptorelin

Second-generation androgen receptor inhibitors, or non-

CancerMPact® Treatment Architecture U.S., Prostate Cancer 4

CancerMPact® Treatment Architecture U.S., Prostate Cancer 5

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CancerMPact® Treatment Architecture U.S., Prostate Cancer 6

United States 2022 United States 2023

United States 2022 United States 2023

Post Definitive Radiotherapy Post Definitive Radiotherapy

Post Systemic Therapy Post Systemic Therapy

No therapy/Observation Active Surveillance Surgery No therapy/Observation Active Surveillance Surgery

United States 2022 United States 2023

No therapy/Observation Active Surveillance No therapy/Observation Active Surveillance

United States 2022 United States 2023

Initial therapy enzalutamide, leuprolide enzalutamide, leuprolide

abiraterone, prednisone, leuprolide enzalutamide, leuprolide

United States 2022 United States 2023

Second-line for abiraterone, prednisone Second-line for abiraterone, prednisone

cabazitaxel, steroid docetaxel

Summary of observed treatment shifts in 2023

CancerMPact® Treatment Architecture U.S., Prostate Cancer 13

Treatment Pathway for Stage I nmHSPC

INITIAL THERAPY OUTCOMES OF INITIAL THERAPY RECURRENCE

Stage I Systemic Therapy HSPC Metastatic recurrence

Treatment Pathway for Stage II nmHSPC

INITIAL THERAPY OUTCOMES OF INITIAL THERAPY RECURRENCE

Stage II Systemic Therapy HSPC Metastatic recurrence

Treatment Pathway for Stage III nmHSPC

INITIAL THERAPY OUTCOMES OF INITIAL THERAPY RECURRENCE

bicalutamide, leuprolide 13.4%

Treatment Pathway for Stage IV (M0) nmHSPC

INITIAL THERAPY OUTCOMES OF INITIAL THERAPY RECURRENCE

Stage IV (M0) Systemic Therapy HSPC Metastatic recurrence

Treatment Pathway for Newly-Recurrent nmHSPC

INITIAL THERAPY RECURRENCE

No therapy/Observation (6.2%) Systemic therapy alone (49.5%)

Active therapy (87.6%) Surgery alone (10.0%)

No therapy/Observation (6.1%) Systemic therapy alone (34.2%)

leuprolide 24.7% enzalutamide, leuprolide 29.0%

Treatment Pathway for nmCRPC

INITIAL THERAPY OUTCOMES OF INITIAL THERAPY RECURRENCE

Remain untreated until development of mCRPC (41.6%)

Initial Systemic Therapy for Newly-Developed nmCRPC

Treatment Pathway for mHSPC

Systemic therapy alone Progress to CRPC (34.0%) Progress to CRPC (41.6%)

Long-term response (17.5%) Long-term response (12.5%)

Initial Systemic Therapy mHSPC Systemic Therapy for Second-Line mHSPC

Treatment Pathway for mCRPC

INITIAL THERAPY OUTCOMES OF OUTCOMES OF

Systemic therapy alone