GU 報告

Journal Presenter: PGY1 周恩如
Reading
Supervisor: VS 游智欽
February 2024
Conclusion
 In the intermediate-risk group, Longer PFS and OS:
IO + TKI > IO+IO
 In the poor-risk group: no significant difference in

PFS or OS between 2 combinations
Overall survival (OS); progression-free survival (PFS); tyrosine kinase inhibitors (TKIs); immune oncology
(IO); International Metastatic Renal Cell Carcinoma Database Consortium(IMDC)
Introduction
 Of the RCC patients, 25–30% have metastases at the time of diagnosis, and around
30% relapse with distant metastases after surgical approaches
 At present, nivolumab + ipilimumab has been approved by the US FDA in patients

with intermediate and poor International Metastatic Renal Cell Carcinoma Database
Consortium (IMDC) risk class
 ARON-1 study (NCT05287464, June 2023) : OS was longer with IO+TKI compared
with IO+IO therapy
Method
 Aged ≥18 yr with a histologically confirmed diagnosis of RCC, and
histologically or radiologically confirmed metastatic disease
 January 1, 2016 ～ October 1, 2022, from 58 centers in 20 countries
 Intervention: IO + TKI or IO + IO
 RECIST 1.1 criteria: Tumor radiological assessment
 Primary outcome: OS and PFS
RESULT
OS and PFS in intermediate and poor IMDC treated by immune combinations
51.6 mo
17.3 mo
18.4 mo
11.6 mo
intermediate-risk mRCC
OS in intermediate
IMDC treated by
immune combinations
Poor-risk mRCC
OS in poor
IMDC treated by
immune
combination
p = 0.047
p < 0.001
p = 0.613
p = 0.614
OS and PFS in
intermediate or poor
IMDC risk treated
by IO + TKI or IO + IO
Discussion
 IMDC Intermediate risk group: longer PFS and OS in received IO + TKI compared
with IO+IO → HIF-VEGF pathway
 IMDC Poor-risk group: no difference between IO + TKI and IO+IO

→ main pathway involves stromal-immune/context T cells
 COSMIC 313 trial(ESMO 2022): cabozantinib + nivolumab + ipilimumab, but poor-

risk group have no benefit from the addition of cabozantinib (HR 1.04)
Limitation
 Retrospective nature
 A centralized review of radiological imaging was not performed, and
patients not assessable for a response were excluded
 No available data on concomitant medications or other comorbidities
that affect the efficacy of 1st-line therapy
 Follow-up time limitation for OS, included a 6-mo OS landmark analysis
(S2) > results need larger prospective validation
Conclusion
 In the intermediate-risk group, Longer PFS and OS:

IO + TKI > IO+IO
 ipilimumab + nivolumab
January 2024
Conclusion
 BrM screening may be warranted as part of the initial assessment
 First-line IO-based combination therapy associated with better

prognosis, compare with tyrosine kinase inhibitor monotherapy
brain metastases (BrM); immuno-oncology (IO); metastatic renal cell carcinoma (mRCC)
Introduction
• Brain metastases (BrM) have global prevalence of 7.3% on initiation of
systemic therapy for metastatic renal cell carcinoma (mRCC)
• Systemic therapies are the mainstay of treatment for patients with BrM, focal
therapies are also used because of the poor brain penetration of therapeutic agents
• There has been a move towards stereotactic radiotherapy (SRT) instead of

conventional whole-brain radiotherapy (WBRT) owing to better tolerability
(IO); International Metastatic Renal Cell Carcinoma Database Consortium(IMDC) ; stereotactic
radiotherapy (SRT); whole-brain radiotherapy (WBRT)
Methods
 A total of 5918 patients with mRCC who received first-line therapies were
screened in the IMDC database (January 2014 ~December 2022)
 IO-based regimen vs TKI regimen ; SRT vs WBRT
 Primary outcome: overall survival
(IO); International Metastatic Renal Cell Carcinoma Database Consortium(IMDC) ; stereotactic
radiotherapy (SRT); whole-brain radiotherapy (WBRT)
RESULT
Kaplan–Meier curves for overall survival
32.7 mo 31.4 mo
34.7 mo
22.8 mo 20.6 mo 16.5 mo
with or without BrM BrM by 1st-line therapies received BrM by focal therapies received
IO = immuno-oncology; brain metastases (BrM); SRT = stereotactic radiotherapy; TKI = tyrosine kinase inhibitor; WBRT = whole-brain radiotherapy.
Receipt of IO-based regimen and receipt of SRT or neurosurgery were independently associated
with longer OS, as was IMDC favorable or intermediate risk
Discussion
• 5% asymptomatic BrM on screening for clinical trials, justifying full disease
assessment including routine brain imaging at baseline
• Frequency of high tumor mutational burden was highest for CNS metastases among
all metastatic sites examined, partly explain the activity of IO-based combination
therapy for BrM
• Focal therapies are the mainstay for BrM given that systemic therapies are
traditionally ineffective for intracranial disease because the blood-brain barrier
significantly limits the penetration of therapeutic agents
Limitation
 Retrospective nature
 Unavailability of PD-L1 expression or intracranial/extracranial disease
status
 Participants from academic centers in high-income countries

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Journal Presenter: PGY1 周恩如

 In the poor-risk group: no significant difference in

 At present, nivolumab + ipilimumab has been approved by the US FDA in patients

 IMDC Poor-risk group: no difference between IO + TKI and IO+IO

 COSMIC 313 trial(ESMO 2022): cabozantinib + nivolumab + ipilimumab, but poor-

 In the intermediate-risk group, Longer PFS and OS:

 First-line IO-based combination therapy associated with better

• There has been a move towards stereotactic radiotherapy (SRT) instead of

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