Pembrolizumab for previously treated, microsatellite instability-high/mismatch repair-deficient advanced colorectal cancer: final analysis of KEYNOTE-164
- PMID: 37141828
- DOI: 10.1016/j.ejca.2023.02.016
Pembrolizumab for previously treated, microsatellite instability-high/mismatch repair-deficient advanced colorectal cancer: final analysis of KEYNOTE-164
Abstract
Background: Pembrolizumab demonstrated durable clinical benefit and manageable safety in previously treated advanced or metastatic microsatellite instability-high (MSI-H)/mismatch repair deficient (dMMR) colorectal cancer (CRC) in the phase 2 KEYNOTE-164 study. Results from the final analysis are presented.
Methods: Eligible patients had unresectable or metastatic MSI-H/dMMR CRC and ≥2 prior systemic therapies (cohort A) or ≥1 prior systemic therapy (cohort B). Patients received pembrolizumab 200 mg intravenously every 3 weeks for ≤35 cycles. The primary end-point was objective response rate (ORR) assessed per Response Evaluation Criteria in Solid Tumors, version 1.1 by blinded independent central review. Secondary end-points included duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety and tolerability.
Results: Sixty-one patients in cohort A and 63 patients in cohort B were enroled; median follow-up was 62.2 months and 54.4 months, respectively. ORR was 32.8% (95% CI, 21.3%-46.0%) in cohort A and 34.9% (95% CI, 23.3%-48.0%) in cohort B. Median DOR was not reached (NR) in either cohort. Median PFS was 2.3 months (95% CI, 2.1-8.1) in cohort A and 4.1 months (95% CI, 2.1-18.9) in cohort B. Median OS was 31.4 months (95% CI, 21.4-58.0) in cohort A and 47.0 months (95% CI, 19.2-NR) in cohort B. No new safety signals were observed. Nine patients who initially responded experienced disease progression off therapy and received second-course pembrolizumab. Six patients (66.7%) completed an additional 17 cycles of pembrolizumab, and 2 patients achieved a partial response.
Conclusions: Pembrolizumab continued to show durable antitumor activity, prolonged OS, and manageable safety in patients with previously treated MSI-H/dMMR CRC.
Clinical trial registry information: ClinicalTrials.gov, NCT02460198.
Keywords: Colorectal cancer; Microsatellite instability; Mismatch repair; Pembrolizumab.
Copyright © 2023. Published by Elsevier Ltd.
Conflict of interest statement
Conflict of interest statement The authors declare the following financial interests/personal relationships, which may be considered as potential competing interests: DTL reports honoraria from MSD; consulting or advisory roles for MSD, Bristol Myers Squibb, Nouscom, Janssen, G1 Therapeutics, and Merus; research funding from MSD, Bristol Myers Squibb, Aduro Biotech, Curegenix, Medivir, and Nouscom; and being listed as an inventor for a patent related to technology for mismatch repair deficiency for diagnosis and therapy (WO2016077553A1). LAD reports consulting or advisory roles for PetDx, Innovatus Capital Partners, Se’er, Delfi, Kinnate, and NeoPhore; equity interests in Epitope, Jounce Therapeutics, Thrive Detect, Se’er, Delfi, Kinnate, NeoPhore and PetDx; positions on the board of directors of Jounce Therapeutics and Epitope; intellectual property interests in multiple licensed patents related to technology for circulating tumour DNA analyses and mismatch repair deficiency for diagnosis and therapy; and a spouse with an equity interest in Amgen. TWK reports research funding from Roche/Genentech paid to his institution. EVC reports consulting or advisory roles for AbbVie, Array Pharma, Astellas, AstraZeneca, Bayer, BeiGene, Biocartis, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Daiichi Sankyo, Halozyme, GlaxoSmithKline, Incyte, Ipsen, Janssen Research, Lilly, MSD, Merck KGaA, Mirati, Novartis, Pierre Fabre, Roche, Seattle Genetics, Servier, Sirtex, Terumo, Taiho, TRIGR, and Zymeworks; and research funding from Amgen, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Ipsen, Lilly, MSD, Merck KGaA, Novartis, Roche, and Servier paid to his institution. RGe reports honoraria from Medison, Roche, Janssen, MSD, and Pfizer; consulting or advisory roles for Eisai, AstraZeneca, Bayer, MSD, BOL Pharma, Ranium, JNJ, and Roche; travel and accommodation expenses from Takeda; a leadership role at Pyxis (Medical Lead); and equity interests in BOL Pharma and Pyxis Oncology. DJ reports honoraria from SKK Kliniken Heilbronn GmbH, Georg Thieme Verlag, Terrapinn, Touch Medical Media, BMS GmbH & Co, KGaA, MSD, Guppe 5 Fileproduktion GmbH, AstraZeneca GmbH, Department of Radiation Medicine, University of Kentucky, and The Norwegian Cancer Society Oslo; consulting or advisory roles for CureVac AG, Definiens, F. Hoffmann-La Roche, Genmab A-S, Life Science Inkubator GmbH, VAXIMM AG, OncoOne Research & Development GmbH, Oncolytics Biotech Inc., Zelluna, HDIT GmbH, AYOXXA, Seattle Genetics, BreakBio Corp., and Roche Pharma AG; expert testimony for courts, Wilhelm-Sander-Stiftung, Else Kröner-Fresenius-Stiftung, Schering Stiftung, and Nordforsk; a leadership role at BMS Stiftung Immunonkologie; and travel accommodation expenses from Amgen Inc, Oryx GmbH, Roche Glycart AG, Parexel.com, IKTZ HD GmbH, BMS. HH reports honoraria from Asahi Kasei, Bayer, Bristol Myers Squibb, Chugai, Daiichi Sankyo, Kyowa Hakko Kirin, Lilly, MSD Biopharma, MSD, Ono, Sanofi, Taiho, Takeda, and Yakult; consulting or advisory roles for Bristol Myers Squibb, Boehringer Ingelheim, Daiichi Sankyo, Dainippon Sumitomo Pharma, MSD, and Ono; and research grants from Amgen, Astellas, AstraZeneca, Bayer, BeiGene, Boehringer Ingelheim, Chugai, Daiichi Sankyo, Dainippon Sumitomo Pharma, Eisai, Incyte, Janssen, MSD Biopharma, MSD, Ono, and Taiho. MB reports honoraria, consulting or advisory roles, and travel and accommodation expenses for MSD. PK reports consulting or advisory roles for MSD and BMS; expert testimony for BMS; and research grant from MSD and BMS paid to his institution. TY reports honoraria from Taiho, Chugai, Eli Lilly, MSD Biopharma, Bayer, MSD, and Ono; and research grants from Taiho, Ono, Chugai, Amgen, Parexel International, Sanofi, Pfizer Japan, MSD, Genomedia Inc., Sysmex, Nippon Boehringer Ingelheim, and Daiichi Sankyo paid to his institution. RGu reports honoraria from Amgen, Servier, Roche, Ipsen, MSD and BMS; and advisory or consultancy for AAA Pharmaceutical, MSD, BMS, Servier, and P Fabre. HT reports honoraria from Taiho, Takeda, Chugai, Eli Lilly, and MSD Biopharma; and research funding from Taiho, Takeda, Chugai, and Daiichi-Sankyo paid to his institution. EE reports consulting or advisory roles for Amgen, Pierre Fabre, Bayer, MSD, F. Hoffmann-La Roche, Merck Serono, Organon, Sanofi, and Servier; and research grants from Amgen, Array Pharma, AstraZeneca, BeiGene, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Debiopharm, Genentech, HalioDx SAS, F. Hoffmann-La Roche, Hutchison, Janssen-Cilag, MedImmune, Menarini, Merck KGaA, MSD, Merus, Mirati, Novartis, Pfizer, PharmaMar, Sanofi Aventis, and Taiho; travel and accommodation expenses from Amgen, Bayer, F. Hoffman-La Roche, Merck Serono, MSD, Novartis, Organon, Pierre Fabre, Sanofi, and Servier; and non-remunerated activities with ASCO, ESMO, and SEOM. SEAB reports consulting or advisory roles for AstraZeneca, Bristol Myers Squibb, Daiichi Sankyo, Immutep, Lilly, and MSD; speaker bureau for Bristol Myers Squibb, Lilly, and MCI Deutschland GmbH; a leadership role at Institut für Klinische Krebsforschung IKF GmbH; equity interests in Institut für Klinische Krebsforschung IKF GmbH; and research funding from AstraZeneca, Bristol Myers Squibb, Celgene, Eurozyto, Hospira, Immutep, Lilly, Medac, Roche, and Vifor. PMB reports advisory and consulting roles for MSD, Pfizer, Bayer, Guardant Health, and Merrimack; and research grants from AbbVie, Boehringer Ingelheim, Ipsen, Processa, Taiho, MacroGenics, and Merck. YC and PL report employment by MSD, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. PM reports employment by and equity interests in MSD, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. TA reports honoraria from Amgen, AstraZeneca, Bristol Myers Squibb, GlaxoSmithKline, MSD, Pierre Fabre, Roche/Ventana, Sanofi, and Servier; consulting or advisory roles for Amgen, Aptitude Health, Astellas Pharma, Bristol Myers Squibb, GamaMabs Pharma, Gilead, Gritstone Oncology, MSD, Kaleido Biosciences, Pierre Fabre, Seagen, Servier, and Transgène; speaker’s bureaus for Bristol Myers Squibb, MSD, Seagen, and Servier; research funding from Bristol Myers Squibb and MSD; travel and accommodation expenses from MSD and Bristol Myers Squibb; and non-remunerated activities for the ARCAD Foundation and GERCOR Group. BON has declared no conflicts of interest.
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