LAUSR

Abstract Background Pembro is approved for microsatellite instability-high (MSI-H)/dMMR CRC that has progressed on fluoropyrimidine+oxaliplatin+irinotecan (Fp+Ox+Ir), based in part on data from the ongoing phase 2 KEYNOTE-164 study (NCT02460198). The outcomes of the Japan (Jpn) subgroup of patients (pts) with dMMR CRC are reported. Methods Pts with metastatic MSI-H/dMMR CRC with ≥2 lines of standard therapy (Fp+Ox+Ir ± anti-VEGF or anti-EGFR; cohort A) or ≥ 1 prior line of therapy (cohort B) received pembro 200 mg every 3 weeks for 2 years or until progression or unacceptable toxicity. Response was assessed every 9 weeks per RECIST v1.1. Primary end point was objective response rate (ORR); secondary end points were duration of response (DOR), disease control rate, progression-free survival (PFS), overall survival (OS), and safety. Data cutoff was February 10, 2017 (cohort A) and September 12, 2017 (cohort B). Results Of the 124 enrolled pts, the Jpn subgroup comprised 7/61 pts in cohort A (cohort AJpn) and 6/63 pts in cohort B (cohort BJpn). At data cutoff, median follow-up was 13.2 months/13.2 months for cohorts A/AJpn and 12.6 months/13.6 months for cohorts B/BJpn. ORRs were 28% (95% CI, 20-44; 17 partial responses [PRs]) and 29% (95% CI, 4-71; 2 PRs) for cohorts A and AJpn, respectively, and 32% (95% CI, 21-45; 2 complete responses and 18 PRs) and 67% (95% CI, 22-96; 4 PRs) for cohorts B and BJpn, respectively. Median DOR was not reached for any group. 12-month PFS rates were 34%/29% for cohorts A/AJpn and 41%/67% for cohorts B/BJpn. 12-month OS rates were 72%/57% and 76%/100%, respectively. Treatment-related adverse events tended to occur more frequently in the Jpn subgroups than in the overall cohorts (57%/71% in cohorts A/AJpn and 64%/83% in cohorts B/BJpn), but the difference was not statistically significant. There were no treatment-related deaths. Conclusions Pembro provided safe and durable antitumor activity, even in the Jpn subgroup, with no new safety signals.