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Mini oral session - Genitourinary tumours, prostate

1771MO - Pembrolizumab (pembro) plus enzalutamide (enza) for patients (pts) with metastatic castration-resistant prostate cancer (mCRPC): Randomized double-blind phase III KEYNOTE-641 study

Date

22 Oct 2023

Session

Mini oral session - Genitourinary tumours, prostate

Topics

Tumour Site

Prostate Cancer

Presenters

Julie Graff

Citation

Annals of Oncology (2023) 34 (suppl_2): S954-S1000. 10.1016/S0923-7534(23)01946-4

Authors

J.N. Graff1, M. Burotto2, P.C. Fong3, D. Pook4, B. Zurawski5, R. Manneh Kopp6, J.E. Salinas7, K. bylow8, G. Kramer9, R. Ratta10, M. Kwiatkowski11, M. Retz12, C. Kwak13, J.A. Arranz Arija14, H.P. Gurney15, N. Matsubara16, L.W. Liang17, J. Todoric17, K. Imai17, A. Stenzl18

Author affiliations

  • 1 Hematology/oncology Department, OHSU - Oregon Health Science University, 97239-3098 - Portland/US
  • 2 Medical Oncology Dept., Bradford Hill-Clinical Center, 8420383 - Recoleta/CL
  • 3 Medical Oncology Dept., Auckland City Hospital, 1023 - Auckland/NZ
  • 4 Oncology Department, Monash Health - Monash Medical Centre, 3168 - Clayton/AU
  • 5 Oncology, Prof. Franciszek Łukaszczyk Oncology Centre, Bydgoszcz/PL
  • 6 Medical Oncology Department, Sociedad de Oncologia y Hematologia Del Cesar, 200001 - Valledupar/CO
  • 7 Oncology, Hospital Provincial de Córdoba, 14004 - Cordoba/ES
  • 8 Medical Oncology, Froedtert Hospital & Medical College of Wisconsin, 53226 - Milwaukee/US
  • 9 Urology, Medical University of Vienna, 1090 - Vienna/AT
  • 10 Medical Oncology Department, Hopital Foch, 92151 - Suresnes/FR
  • 11 Oddział Dzienny Chemioterapii, Szpital Wojewódzki im. Mikolaja Kopernika w Koszalinie, 75-581 - Koszalin/PL
  • 12 Urology, Rechts der Isar Medical Center, Technical University Munich, 80636 - Munich/DE
  • 13 Urology, Seoul National University - College of Medicine - Yeongeon Medical Campus, 03080 - Seoul/KR
  • 14 Medical Oncology, Hospital General Universitario Gregorio Maranon, 28007 - Madrid/ES
  • 15 Medical Oncology, Macquarie University - Faculty of Medicine, Health and Human Sciences, 2109 - Sydney/AU
  • 16 Medical Oncology Department, National Cancer Center Hospital East, 277-8577 - Kashiwa/JP
  • 17 Oncology, Merck & Co., Inc., 07065 - Rahway/US
  • 18 Urology Department, Crona Kliniken - Universitätsklinikum Tübingen, 72076 - Tübingen/DE

Resources

This content is available to ESMO members and event participants.

Abstract 1771MO

Background

Pts with mCRPC with progressive disease (PD) during 2nd generation hormonal agent therapy typically receive chemo next. Additional therapies are needed in this setting. Pembro + enza had antitumor activity in pretreated mCRPC in early phase studies. KEYNOTE-641 (NCT03834493) evaluated pembro + enza vs placebo (pbo) + enza in pts with chemo-naïve mCRPC with/without prior abiraterone (abi).

Methods

Eligible pts were male, aged ≥18 years, had ECOG PS ≤1, had confirmed mCRPC with no prior chemo except docetaxel in the hormone-sensitive setting, and had intolerance to or PD during prior abi or no prior abi. Pts were randomized 1:1 to pembro 200 mg or pbo IV Q3W for ≤35 cycles + enza 160 mg orally daily. Dual primary endpoints were overall survival (OS) and radiographic progression-free survival (rPFS) per PCWG-modified RECIST 1.1 by blinded independent central review. Time to initiation of first subsequent anticancer therapy (TFST) was a key secondary endpoint. Safety/tolerability was a secondary endpoint.

Results

1244 pts were enrolled between Aug 21, 2019, and Jun 10, 2022 (n=621 to pembro + enza; n=623 to pbo + enza). As of Dec 12, 2022, the median (range) follow-up time at first prespecified interim analysis was 27.6 mo (6.1–39.8). 60.9% of all pts had prior abi and 29.1% had prior docetaxel, balanced between arms. The dual primary endpoints of rPFS (median 10.4 mo with pembro + enza vs 9.0 mo with pbo + enza; HR 0.98, 95% CI 0.84−1.14; P=0.41) and OS (median 24.7 mo vs 27.3 mo; HR 1.04, 95% CI 0.88−1.22; P=0.66) were not met. The prespecified boundary for futility for OS was crossed and the study was stopped. Median TFST was 13.2 mo vs 12.6 mo, respectively (HR 0.95, 95% CI 0.83−1.09). Any-grade and grade ≥3 treatment-related AEs occurred in 77.9% and 31.2% of 615 pts with ≥1 dose pembro + enza and 61.6% and 10.8% of 620 pts with ≥1 dose pbo + enza. 3 treatment-related deaths occurred with pembro + enza and none with pbo + enza.

Conclusions

Pembro + enza did not significantly improve efficacy outcomes vs pbo + enza in pts with mCRPC with/without prior abi. Pembro + enza was associated with more treatment-related AEs vs pbo + enza; no new safety signals were observed.

Clinical trial identification

NCT03834493.

Editorial acknowledgement

Writing assistance was provided by Ina Nikolaeva of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. Astellas provided the enzalutamide for this study.

Legal entity responsible for the study

Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

Funding

Funding for this research was provided by Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

Disclosure

J.N. Graff: Financial Interests, Personal, Invited Speaker, CME vendor: P3; Financial Interests, Personal, Invited Speaker, CME: Binaytara Foundation; Financial Interests, Personal, Other, Testicular cancer chair- make around $7,000 USD per year: Elsevier; Financial Interests, Personal, Other, Testicular cancer chair: Elsevier; Financial Interests, Institutional, Coordinating PI, Two Investigator initiated, lead in a phase 3 trial (KN 641), local PI for several studies: Merck Sharpe Dohme; Financial Interests, Institutional, Steering Committee Member: Janssen, Curium; Financial Interests, Institutional, Coordinating PI: Sanofi; Non-Financial Interests, Leadership Role: Veterans Affairs Hospital. M. Burotto: Financial Interests, Personal, Invited Speaker: AstraZeneca, BMS; Financial Interests, Personal, Advisory Board: Merck & Co., Inc., Roche. P.C. Fong: Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Other, Oncology meeting attendance/Accommodation: Pfizer; Non-Financial Interests, Advisory Role: New Zealand Prostate Cancer Foundation. D. Pook: Financial Interests, Personal, Invited Speaker: Bayer; Financial Interests, Personal, Advisory Board: BMS, MSD, Ipsen, Pfizer, Eisai, Astellas; Financial Interests, Institutional, Invited Speaker: BMS, Astellas, Pfizer, Roche, Ipsen, MSD, Amgen. R. Manneh Kopp: Financial Interests, Personal, Invited Speaker: MSD, AstraZeneca, BMS, Janssen, Astellas, Pfizer, Bayer, Eli Lilly, Roche, Tecnofarma, Procaps; Financial Interests, Personal, Advisory Board: MSD, Bayer, Tecnofarma; Financial Interests, Personal and Institutional, Invited Speaker: MSD, Bayer, BMS, Roche, Pfizer, Novartis, AstraZeneca; Non-Financial Interests, Leadership Role: Asociación Colombiana de Hematología y Oncología. G. Kramer: Financial Interests, Personal, Advisory Board: Astellas, AstraZeneca, Bayer, Janssen, Pfizer, Sandoz; Financial Interests, Personal, Advisory Role: Ferring, MSD, Novartis; Financial Interests, Personal, Other, Travel Expenses: Astellas, AstraZeneca, Bayer, Janssen, MSD, Novartis. R. Ratta: Financial Interests, Personal, Invited Speaker: Ipsen, Astellas; Financial Interests, Personal, Advisory Board: Pfizer, Merck, BMS, AstraZeneca. M. Kwiatkowski: Financial Interests, Personal, Invited Speaker: Janssen Cilag, Novartis, Roche; Non-Financial Interests, Principal Investigator, Clinical Trials: MSD, BMS; Non-Financial Interests, Principal Investigator, Clinical trials: AstraZeneca, Roche, Hengrui, Janssen Cilag, BeiGene, Shanghai Jinshu, Bayer. M. Retz: Financial Interests, Personal, Research Grant: BMS. J.A. Arranz Arija: Financial Interests, Personal, Advisory Board: Astellas, BMS, Merck, Pfizer, Bayer, MSD, Eisai; Financial Interests, Personal, Invited Speaker: Astellas; Financial Interests, Institutional, Invited Speaker, SOGUG: BMS. H.P. Gurney: Financial Interests, Personal, Advisory Board: Merck, Pfizer, AstraZeneca, BMS, MSD, Ipsen, Astellas. N. Matsubara: Financial Interests, Personal, Invited Speaker: Sanofi; Financial Interests, Institutional, Invited Speaker: Janssen, AstraZeneca, Bayer, Roche, MSD, Taiho, Astellas, Amgen, Eisai, Eli Lilly, Pfizer, Chugai, AbbVie. L.W. Liang, J. Todoric, K. Imai: Financial Interests, Personal, Full or part-time Employment: Merck & Co., Inc.; Financial Interests, Personal, Stocks/Shares: Merck & Co., Inc.. A. Stenzl: Financial Interests, Personal, Advisory Board: Astellas, Pfizer, Bayer, Ipsen Pharma, Roche Pharma, AstraZeneca, Cystotech, GSK, MSD; Non-Financial Interests, Other, Preparation of an official project related to connection between Hospitals/doctors and Industry in general, Z.I.M.T: BioRegioSTERN; Non-Financial Interests, Leadership Role, Secretary General: European Assoc. of Urology (EAU); Non-Financial Interests, Leadership Role, Member Board of Directors: European Cancer Organisation. All other authors have declared no conflicts of interest.

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