2023 Endocrine Pretreated HR Neg MBC Rapid Update Slides

Chemotherapy and Targeted Therapy for
Endocrine-Pretreated or Hormone Receptor–Negative

Metastatic Breast Cancer
ASCO Guideline Rapid Recommendation Update
Moy, B et al.
www.asco.org/breast-cancer-guidelines ©American Society of Clinical Oncology (ASCO) 2023. All rights reserved worldwide.
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2
Overview
1. Background & Methodology
• Introduction
• Development Methodology
2. Rapid Recommendation Update
3. Summary of Previous Recommendations
4. Additional Information
• Additional Resources
• Expert Panel Members
• Abbreviations
1 Background & Methodology
4
Introduction
• In 2021, ASCO published a guideline on chemotherapy and targeted therapy for patients
with human epidermal growth factor receptor 2 (HER2)–negative metastatic breast cancer
that is either endocrine-pretreated or hormone receptor-negative.1
• That guideline was updated in August 2022 to incorporate the results of the DESTINY-
Breast04 trial.2
• The results of the TROPiCS-023 trial, published on October 10, 2022, provided another
signal to update.
5
Development Methodology
• A targeted electronic literature search was conducted to identify any additional phase III
RCTs of treatment options in this patient population. No additional RCTs were identified.
• The original guideline Expert Panel was reconvened to review new evidence from
TROPiCS-023 and to review and approve the revised recommendation.
• The ASCO Guideline methodology manual can be found at: www.asco.org/guideline-
methodology
2 Rapid Recommendation Update
7
Rapid Recommendation Update
Updated Recommendation Evidence-based

benefits outweigh harms
• Patients with hormone receptor-positive HER2-negative Evidence Quality

Strength of
Recommendation
metastatic breast cancer who are refractory to endocrine Moderate Strong
therapy and have received at least 2 prior lines of chemotherapy
for metastatic disease may be offered sacituzumab govitecan.
3 Summary of Previous
Recommendations
9
Summary of Recommendations
Rapid Recommendation 2022 Evidence-based

• Patients with HER2 IHC 1+ or 2+ and ISH negative metastatic Evidence Quality
Strength of
Recommendation
breast cancer who have received at least one prior Moderate Strong
chemotherapy for metastatic disease, and if HR+ are refractory
to endocrine therapy, should be offered treatment with
trastuzumab deruxtecan.
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Clinical Question 1
• Is there an optimal sequence of chemotherapy and/or targeted therapy (first-line, second-line
or greater) for patients with triple negative metastatic breast cancer (with or without BRCA1
or BRCA2 germline mutations)?
Recommendation 1.1
• Patients with metastatic triple negative breast cancer with Evidence-based
expression of programmed cell death ligand-1 (PD-L1-positive)
and no existing contraindications may be offered the addition of Strength of
Evidence Quality
immune checkpoint inhibitor to chemotherapy (atezolizumab plus Recommendation
nab-paclitaxel or pembrolizumab plus chemotherapy) as first-line Moderate Strong

therapy.
11
Recommendation 1.2 Evidence-based
• Patients with metastatic triple negative breast cancer without Strength of

Evidence Quality
expression of programmed cell death ligand-1 (PD-L1-negative) Recommendation
should be offered single agent chemotherapy rather than Moderate Strong

combination chemotherapy as first-line treatment, although
combination regimens may be offered for symptomatic or
immediately life-threatening disease for which time may allow only
one potential chance for therapy.
Practical Information
• Patients may be offered either platinum-based or non-platinum-based regimens based on
individualized patient and provider assessment of preferences, risks, and benefits.
12
• Patients with metastatic triple negative breast cancer who have Strength of
Evidence Quality
received at least two prior therapies for metastatic disease should Recommendation
be offered treatment with sacituzumab govitecan. High Strong
13
Recommendation 1.4
Evidence-based
• Patients with metastatic triple negative breast cancer with benefits outweigh harms
germline BRCA1 or 2 mutations who have previously been treated Strength of

Evidence Quality
with chemotherapy in the neoadjuvant, adjuvant, or metastatic Recommendation
disease setting may be offered an oral PARP inhibitor (olaparib or Moderate Strong
talazoparib) rather than chemotherapy.
• Small single-arm studies show that oral PARP inhibitor therapy demonstrates high response
rates in metastatic breast cancer encoding DNA repair defects, such as germline PALB2
mutation carriers and somatic BRCA mutations. It should also be noted that the randomized
PARP inhibitor trials made no direct comparison with taxanes, anthracyclines, or platinums;
comparative efficacy against these compounds is unknown.
14
Clinical Question 2
• What are the indications for chemotherapy versus endocrine therapy in endocrine-pretreated
ER-positive metastatic breast cancer?

• Patients with metastatic hormone receptor-positive (HR-positive)

breast cancer with disease progression on a prior endocrine agent Evidence Quality Strength of
Recommendation
with or without targeted therapy may be offered treatment with
Moderate Strong
either endocrine therapy with or without targeted therapy (refer to
the companion ASCO guideline on Endocrine Therapy and Targeted Therapy for Hormone
Receptor-Positive Metastatic Breast Cancer12 for details) or single-agent chemotherapy.
• Treatment choice should be based on individualized patient and provider assessment of
preferences, risks, and benefits.
15
Clinical Question 3
• Is there an optimal sequence of non-endocrine agents for patients with hormone receptor-
positive but HER2-negative metastatic breast cancer that are no longer benefiting from
endocrine therapy (with or without BRCA1 or BRCA2 germline mutations)?

• Patients with metastatic HR-positive but HER2-negative breast
cancer with germline BRCA1 or 2 mutations who are no longer Evidence Quality
Strength of
benefiting from endocrine therapy may be offered an oral PARP Recommendation
inhibitor in the first- through to third-line setting rather than Moderate Strong
chemotherapy
16
• Small single-arm studies show that oral PARP inhibitor therapy demonstrates high response
rates in metastatic breast cancer encoding DNA repair defects, such as germline PALB2
mutation carriers and somatic BRCA mutations. It should also be noted that the randomized
PARP inhibitor trials made no direct comparison with taxanes, anthracyclines, or platinums;
comparative efficacy against these compounds is unknown.
17
Recommendation 3.2
Evidence-based
• Patients with HR-positive HER2-negative MBC no longer benefits outweigh harms
benefiting from ET should be offered single-agent chemotherapy Strength of

Evidence Quality
rather than combination therapy, although combination regimens Recommendation
may be offered for symptomatic or immediately life-threatening Moderate Strong

disease for which time may allow only one potential chance for
therapy.
• Choice of chemotherapy agent should be based on individualized patient and provider
assessment of preferences, risks, and benefits.
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Clinical Question 4
• At what point should a patient be transitioned to hospice or best supportive care only?
Recommendation 4.1 Consensus

benefits/harms ratio unknown
• No recommendation regarding at which point a patient’s care Strength of

should be transitioned to hospice or best supportive care only is Evidence Quality
Recommendation
possible at this time. N/A Strong

• Given the heterogeneity of breast cancer and the treatment goals of patients with breast
cancer it is not possible to identify a universal optimal time to transition to hospice or best
supportive care. When to transition is a decision that should be shared between the patient
and clinician in the context of an ongoing conversation regarding goals of care. The
conversation about integration of supportive care and eventual consideration of hospice care
should start early in the management of metastatic breast cancer.
4 Additional Information
20
Additional Resources
• More information, including clinical tools and resources, is
available at www.asco.org/breast-cancer-guidelines
• Patient information is available at www.cancer.net
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Guideline Panel Members

Name Affiliation/Institution
Beverly Moy, MD, MPH co-chair Massachusetts General Hospital, Boston, MA
Lisa A. Carey, MD, ScM co-chair UNC Lineberger Comprehensive Cancer Center, Chapel Hill, NC
Avan Armaghani, MD Moffitt Cancer Center, Tampa, FL
Mariana Chavez-MacGregor, MD, MSc MD Anderson Cancer Center, Houston, TX
Steven E. Come, MD Beth Israel Deaconess Medical Center, Boston, MA
Michael A. Danso, MD Virginia Oncology Associates, Norfolk, VA
Nancy E. Davidson, MD Fred Hutchinson Cancer Research Center and University of Washington, Seattle, WA
Natalie Dickson, MD, MMHC Tennessee Oncology, Nashville, TN
Julie R. Gralow, MD University of Washington, Seattle, WA
Gabriel N. Hortobagyi, MD MD Anderson Cancer Center, Houston, TX
William J. Irvin Jr., MD Bon Secours St. Francis, Midlothian, VA
Heather L. McArthur, MD, MPH Cedars-Sinai, Los Angeles, CA
Rita Nanda, MD University of Chicago, Chicago, IL
Cheryl L. Perkins, MD Dallas, TX
Katherine E. Reeder-Hayes, MD, MBA, MS UNC Lineberger Comprehensive Cancer Center, Chapel Hill, NC
Kathryn J. Ruddy, MD Mayo Clinic, Rochester, MN
Ian E. Smith, MD Royal Marsden Hospital, London, UK
Laura Spring, MD Massachusetts General Hospital, Boston, MA
Sophie S. Turner New York, NY
Paul S. Unger, MD University of Vermont Health Network, Burlington, VT
Shaveta Vinayak, MD Seattle Cancer Care Alliance and University of Washington, Seattle, WA
Douglas Yee, MD University of Minnesota, Minneapolis and Saint Paul, MN
R. Bryan Rumble, MSc American Society of Clinical Oncology (ASCO), Alexandria, VA
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Abbreviations
• ASCO, American Society of Clinical Oncology
• BRCA, Breast Cancer gene
• ER, estrogen receptor
• ET, endocrine therapy
• HER2, human epidermal growth factor receptor 2
• HR+, hormone receptor-positive
• IHC, immunohistochemistry
• ISH, in situ hybridization
• MBC, metastatic breast cancer
• PARP, poly-ADP ribose polymerase
• PD-L1, programmed cell death ligand-1
• RCT, randomized controlled trial
• TPC, treatment of physician’s choice
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References
1. Moy B, Rumble RB, Come SE, et al: Chemotherapy and Targeted Therapy for Patients With Human Epidermal
Growth Factor Receptor 2-Negative Metastatic Breast Cancer That is Either Endocrine-Pretreated or Hormone
Receptor-Negative: ASCO Guideline Update. J Clin Oncol 39:3938-3958, 2021
2. Modi, S., et al. (2022). "Trastuzumab Deruxtecan in Previously Treated HER2-Low Advanced Breast Cancer." N
Engl J Med 387(1): 9-20
3. Rugo HS, Bardia A, Marmé F, et al: Sacituzumab Govitecan in Hormone Receptor–Positive/Human Epidermal
Growth Factor Receptor 2–Negative Metastatic Breast Cancer. Journal of Clinical Oncology 40:3365-3376, 2022
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Disclaimer
The Clinical Practice Guidelines and other guidance published herein are provided by the American Society of Clinical
Oncology, Inc. (ASCO) to assist providers in clinical decision making. The information herein should not be relied upon as
being complete or accurate, nor should it be considered as inclusive of all proper treatments or methods of care or as a
statement of the standard of care. With the rapid development of scientific knowledge, new evidence may emerge
between the time information is developed and when it is published or read. The information is not continually updated and
may not reflect the most recent evidence. The information addresses only the topics specifically identified therein and is
not applicable to other interventions, diseases, or stages of diseases. This information does not mandate any particular
course of medical care. Further, the information is not intended to substitute for the independent professional judgment of
the treating provider, as the information does not account for individual variation among patients. Recommendations
specify the level of confidence that the recommendation reflects the net effect of a given course of action. The use of
words like “must,” “must not,” “should,” and “should not” indicates that a course of action is recommended or not
recommended for either most or many patients, but there is latitude for the treating physician to select other courses of
action in individual cases. In all cases, the selected course of action should be considered by the treating provider in the
context of treating the individual patient. Use of the information is voluntary. ASCO does not endorse third party drugs,
devices, services, or therapies used to diagnose, treat, monitor, manage, or alleviate health conditions. Any use of a brand
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arising out of or related to any use of this information, or for any errors or omissions.

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Chemotherapy and Targeted Therapy for

Endocrine-Pretreated or Hormone Receptor–Negative

Rapid Recommendation Update

Updated Recommendation Evidence-based

• Patients with hormone receptor-positive HER2-negative Evidence Quality

Rapid Recommendation 2022 Evidence-based

nab-paclitaxel or pembrolizumab plus chemotherapy) as first-line Moderate Strong

• Patients with metastatic triple negative breast cancer without Strength of

should be offered single agent chemotherapy rather than Moderate Strong

be offered treatment with sacituzumab govitecan. High Strong

germline BRCA1 or 2 mutations who have previously been treated Strength of

Recommendation 2.1 Evidence-based

• Patients with metastatic hormone receptor-positive (HR-positive)

Recommendation 3.1 Evidence-based

benefiting from ET should be offered single-agent chemotherapy Strength of

may be offered for symptomatic or immediately life-threatening Moderate Strong

Recommendation 4.1 Consensus

• No recommendation regarding at which point a patient’s care Strength of

possible at this time. N/A Strong

• Patient information is available at www.cancer.net

Guideline Panel Members

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