Pembrolizumab Plus mFOLFOX7 or FOLFIRI for Microsatellite Stable/Mismatch Repair-Proficient Metastatic Colorectal Cancer: KEYNOTE-651 Cohorts B and D.

Autor: Kim R; Department of Gastrointestinal Oncology, Moffitt Cancer Center, Tampa, FL. Electronic address: richard.kim@moffitt.org., Tehfe M; Hematology and Medical Oncology Division, Centre Hospitalier de l'Université de Montréal, Montréal, Canada., Kavan P; Department of Medicine and Oncology, Sir Mortimer B. Davis Jewish General Hospital, Segal Cancer Centre, McGill University, Montreal, Canada., Chaves J; Medical Oncology, Northwest Medical Specialties, Tacoma, WA., Kortmansky JS; Section of Medical Oncology, Yale Cancer Center, New Haven, CT., Chen EX; Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, Toronto, Canada., Lieu CH; Division of Medical Oncology, Department of Medicine, University of Colorado School of Medicine, Aurora, CO., Wong L; Division of Hematology and Oncology, Baylor Scott and White, Temple, TX., Fakih M; Department of Medical Oncology and Therapeutics Research, City of Hope Comprehensive Cancer Center, Duarte, CA., Spencer K; Department of Medicine, Perlmutter Cancer Center of NYU Langone Health and Department of Internal Medicine NYU Grossman School of Medicine, New York, NY., Zhao Q; Department of Medical Oncology, BARDS, Merck & Co., Inc., Rahway, NJ., Predoiu R; Department of Medical Oncology, BARDS, Merck & Co., Inc., Rahway, NJ., Li C; Department of Medical Oncology, BARDS, Merck & Co., Inc., Rahway, NJ., Leconte P; Department of Medical Oncology, MSD France, Puteaux, France., Adelberg D; Department of Medical Oncology, Merck & Co., Inc., Rahway, NJ., Chiorean EG; Division of Medical Oncology, Department of Medicine, University of Washington and Fred Hutchinson Cancer Center, Clinical Research Division, Seattle, WA.
Jazyk: angličtina
Zdroj: Clinical colorectal cancer [Clin Colorectal Cancer] 2024 Jun; Vol. 23 (2), pp. 118-127.e6. Date of Electronic Publication: 2024 Apr 01.
DOI: 10.1016/j.clcc.2024.03.001
Abstrakt: Background: The phase 1b KEYNOTE-651 study evaluated pembrolizumab plus chemotherapy in microsatellite stable or mismatch repair-proficient metastatic colorectal cancer.
Patients and Methods: Patients with microsatellite stable or mismatch repair-proficient metastatic colorectal cancer received pembrolizumab 200 mg every 3 weeks plus 5-fluorouracil, leucovorin, oxaliplatin (previously untreated; cohort B) or 5-fluorouracil, leucovorin, irinotecan (previously treated with fluoropyrimidine plus oxaliplatin; cohort D) every 2 weeks. Primary end point was safety; investigator-assessed objective response rate per RECIST v1.1 was secondary and biomarker analysis was exploratory.
Results: Thirty-one patients were enrolled in cohort B and 32 in cohort D; median follow-up was 30.2 and 33.5 months, respectively. One dose-limiting toxicity (grade 3 small intestine obstruction) occurred in cohort D. In cohort B, grade 3 or 4 treatment-related adverse events (AEs) occurred in 18 patients (58%), most commonly neutropenia and decreased neutrophil count (n = 5 each). In cohort D, grade 3 or 4 treatment-related AEs occurred in 17 patients (53%), most commonly neutropenia (n = 7). No grade 5 treatment-related AEs occurred. Objective response rate was 61% in cohort B (KRAS wildtype: 71%; KRAS mutant: 53%) and 25% in cohort D (KRAS wildtype: 47%; KRAS mutant: 6%). In both cohorts, PD-L1 combined positive score and T-cell-inflamed gene expression profiles were higher and HER2 expression was lower in responders than nonresponders. No association between tumor mutational burden and response was observed.
Conclusion: Pembrolizumab plus 5-fluorouracil, leucovorin, oxaliplatin/5-fluorouracil, leucovorin, irinotecan demonstrated an acceptable AE profile. Efficacy data appeared comparable with current standard of care (including by KRAS mutation status). Biomarker analyses were hypothesis-generating, warranting further exploration.
Gov Identifier: ClinicalTrials.gov; NCT03374254.
Competing Interests: Disclosure R. Kim reports honoraria from Taiho; advisory/consultancy roles with Bayer Servier, Ipsen, and Roche; and speakers bureau for Eisai, Pfizer, and Incyte. M. Tehfe reports advisory/consultancy roles with Merck & Co., Inc., Rahway, NJ, USA, BMS, Taiho, and Pfizer; and speakers bureau for BMS and Taiho. P. Kavan reports advisory/consultancy role with Merck; expert testimony for Merck & Co., Inc., Rahway, NJ, USA; and an institutional educational grant to their institution. J. S. Kortmansky reports research funding to their institution from Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, and Genentech. E. X. Chen reports advisory/consultancy roles from AstraZeneca, Eisai, and GSK and research funding to their institution from AstraZeneca, Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, BMS, Novartis, Roche, Zymeworks, and 1Globe. C. H. Lieu reports advisory/consultancy roles with Natera; and research funding to their institution from Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. M. Fakih reports advisory/consultancy roles with AstraZeneca, Bayer, Bristol Myers Squibb, GlaxoSmithKline, Incyte, Mirati, Nouscom, PsiOxus, Roche/Genentech, and Taiho. K. Spencer reports advisory/consultancy roles with QED Therapeutics, Helsinn, Lynx Group, and Caris. Q. Zhao reports stock ownership at Merck & Co., Inc., Rahway, NJ, USA. R. Predoiu, C. Li, P. Leconte, and D. Adelberg report employment with Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. P. Leconte and D. Adelberg report stock ownership at Merck & Co., Inc., Rahway, NJ, USA. E. G. Chiorean reports advisory/consultancy roles with Astellas, Bayer, Cardiff, Foundation, G1 Therapeutics, Ipsen, Noxxon, Novartis, Merck & Co., Inc., Rahway, NJ, USA, Pfizer, and Stemline; research funding to their institution from Aadi, Biosplice, BioMed Valley, Boehringer Ingelheim, Clovis, Corcept, Erasca, Fibrogen, Lona, Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, Novartis, Rafael, and Stemline; and travel/accommodations from G1 Therapeutics. J. Chaves and L. Wong report no conflicts of interest.
(Copyright © 2024 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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