Dr. Joseph Tabernero, MD, discusses the safety profile for Pembrolizumab.
Background: KEYNOTE062 (NCT02494583) was a randomized, active controlled study of 1L P or P+C vs C in pts with PD-L1 combined positive score ?1 (CPS ?1), HER2-negative, advanced GC. Methods: 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. Randomization was stratified by region, disease status, and fluoropyrimidine treatment. 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. Final analysis cutoff date was 26 Mar 2019. Results: 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 10.8 mo; HR 0.69; 95% CI 0.49-0.97) but wasnt 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. P+C did not significantly prolong PFS in CPS ?1. ORR was higher for P+C vs C. Grade 3-5 drug-related AE rates were 17% (P), 73% (P+C), and 69% (C). Conclusions: 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. The safety profile was more favorable for P vs C. Clinical trial information: NCT02494583