Pembrolizumab with or without chemotherapy vs chemotherapy in patients with advanced G/GEJ cancer (GC) including outcomes according to Microsatellite Instability-High (MSI-H) status in KEYNOTE-062

Abstract

Background: KEYNOTE-062 (NCT02494583) was a randomized, study of 1L pembrolizumab (P) or pembro +chemo (P+C) vs chemo (C) in patients (pts) with PD-L1 combined positive score >=1 (CPS >=1), HER2-negative, advanced GC. Method(s): Eligible pts were randomized 1:1:1 to P 200 mg Q3W for up to 2 y, P+C (cisplatin 80 mg/m2+ 5-FU 800 mg/m2/d on d1-d5 Q3W [or capecitabine 1000 mg/m2 BID on d1-d14 Q3W per local guideline]) or placebo Q3W+ C. Primary endpoints were OS in CPS >=1 and CPS >=10 for P+C vs C and P vs C and PFS (RECIST v1.1; central review) in CPS >=1 for P+C vs C. ORR (RECIST v1.1; central review) in CPS >=1 for P+C vs C was the secondary endpoint. The final analysis cutoff date was 26 Mar 2019. Result(s): 763 pts (281 with CPS >=10) were randomized to P+C (257), P (256), or C (250) (Table). Median follow-up was 11.3 mo. P was noninferior to C for OS in CPS >=1 per prespecified margins. P vs C prolonged OS in CPS >=10 (median 17.4 vs 10.8mo; HR 0.69; 95% CI 0.49-0.97) but wasn't tested per analysis plan. P+C vs C was not superior for OS in CPS >=1 or CPS >=10, with a favorable trend for P+C. In an exploratory analysis of pts with MSI-H tumors with CPS >=1 (N=50), median OS was not reached vs 8.5mo for both P vs C (HR 0.29; 95% CI 0.11-0.81) and P+C vs C (HR 0.37; 95% CI 0.14-0.97). PFS was longer with P vs C (HR 0.72; 95% CI 0.31-1.68) and P+C vs C (HR 0.45; 95% CI 0.18-1.11). ORR was higher with P (57%) and P+ C (65%) vs C (37%). Median DOR was 21.2 mo with P, not reached (P +C) vs 7.0 mo (C). Grade 3-5 drugrelated AE rates were 17% (P), 73% (P+C), and 69% (C). Conclusion(s): As 1L therapy for advanced GC, P was noninferior to C for OS in CPS >=1 with clinically meaningful improvement for OS in CPS >=10. P+C did not show superior OS and PFS in CPS >=1 and OS in CPS>=10. Clinical benefit was substantially enhanced in a small subset of pts with MSI-H tumors. The safety profile was more favorable for P vs C. (Table Presented) .