A high level of microsatellite instability (MSI-H) and abnormal expression of MMR proteins is indicative of a dMMR tumor. Prior reports suggest that anti–PD-1 antibody therapy provides durable responses in pts with dMMR cancers. We report primary outcomes from cohort A and the Japan subgroup of the KEYNOTE-164 study of pts with dMMR CRC (NCT02460198).
Pts with metastatic CRC previously treated with standard therapies (fluoropyrimidine, oxaliplatin, and irinotecan), with dMMR or MSI-H confirmed locally by IHC or PCR, were enrolled. Eligible pts received pembro 200 mg Q3W for 2 years or until progression, unacceptable toxicity, or withdrawal of consent. Tumor response was assessed every 9 weeks per RECIST v1.1 by independent review. The primary end point was objective response rate (ORR); secondary end points included duration of response (DOR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety. Data cutoff was Feb 10, 2017.
Of 61 pts enrolled, median age was 53 y in the overall cohort and 51 y in the Japan subgroup; 59% and 43% were male, respectively. Most pts received 2 prior (46% and 29%) or ≥ 3 prior (44% and 71%) lines of therapy. Median duration of follow-up was 13.2 mo (range, 0.2-16.9) in the overall cohort and 13.2 mo (8.0-16.9) in the Japan subgroup. In the overall cohort, ORR was 28% (17 PR; 95% CI, 17-41), DCR was 51% (95% CI, 38-64), and median DOR was NR (range, 2.9+ to 12.5+ mo). The 12-mo PFS and OS rates were 34% and 72%. In the Japan subgroup (n = 7), ORR was 29% (2 PR; 95% CI, 4-71), DCR was 57% (95% CI, 18-90), and median DOR was NR (range, 10.2+ to 10.4+ mo); 12-mo PFS and OS rates were 29% and 57%. Treatment-related AEs occurred in 35/61 (57%) and 5/7 (71%) of the overall cohort and Japan subgroup. Immune-mediated AEs and infusion reactions occurred in 11/61 (18%) and 2/7 (29%), respectively. There were no treatment-related deaths.
Pembro provided durable antitumor activity in heavily pretreated pts with dMMR CRC in the overall cohort and Japan subgroup, with a safety profile consistent with that previously observed for pembro.
Medical writing and/or editorial assistance was provided by Julia Burke, PhD, of the ApotheCom pembrolizumab team (Yardley, PA, USA). This assistance was funded by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.
Clinical trial identification
164-07, Jan 3, 2018 NCT02460198.
Legal entity responsible for the study
Merck & Co., Inc., Kenilworth, NJ, USA.
Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.
H. Hara: Honoraria: Chugai, Taiho, Merck Serono, Yakult Honsha, Lilly, Consulting, Ono, Chugai, Research, AZ, Chugai, Merck Serono, MSD, Ono, Taiho, Takeda, Boehringer Ingelheim, Dainippon Sumitomo, Daiichi Sankyo, Lilly. T. Yoshino: Research Funding Sumitomo Dainippon Pharma Co., Ltd. H. Taniguchi: Grants: Takeda; Personal fees: Chugai, Taiho. K. Shitara: Honoraria: Novartis, AbbVie, Yakult; Consulting: Astellas, Lilly, BMS, Takeda, Pfizer, Ono; Research: Dainippon Sumitomo, Lilly, MSD, Daiichi Sankyo, Taiho, Chugai, Ono. Y. Kuboki: Grants: Taiho, Daiichi-Sankyo, Takeda, AstraZeneca, Incyte; Personal fees: Taiho. T. Shimamoto, K. Ueki: Employment, stock ownership: Merck & Co., Inc. S.R. Han, K. Noguchi: Employment, stock ownership: MSD K.K. L.A. Diaz: Employment, stock ownership: Personal Genome Diagnostics; Travel: Merck; Royalties/patents/intellecutal property: Personal Genome Diagnostics, PapGene, Inostics. All other authors have declared no conflicts of interest.