Efficacy of Pembrolizumab Monotherapy for Advanced Gastric/Gastroesophageal Junction Cancer with Programmed Death Ligand 1 Combined Positive Score {greater than or equal to}10

Abstract

Purpose: Pembrolizumab demonstrated efficacy in PD-L1-positive (combined positive score [CPS] {greater than or equal to}1) advanced gastric/gastroesophageal junction (G/GEJ) cancer in the first-, second-, and third-line setting in KEYNOTE-062, KEYNOTE-061, and KEYNOTE-059, respectively. To better delineate the specificity of CPS as a predictor of clinical outcomes, we analyzed pembrolizumab efficacy in patients with CPS{greater than or equal to}10 in these trials. Experimental Design: Included were patients with CPS{greater than or equal to}10 tumors from KEYNOTE-059 cohort 1 (pembrolizumab, n=46; post hoc), KEYNOTE-061 (pembrolizumab, n=53; chemotherapy, n=55; post hoc), and KEYNOTE-062 (pembrolizumab, n=92; chemotherapy, n=90; primary). Efficacy outcomes were OS, PFS, ORR, and DOR. Results: In KEYNOTE-059 median follow-up was 6 months, median OS was 8 months (95% CI, 5.8-11.1), ORR was 17%, and median (range) DOR was 21 months (3+-35+). In KEYNOTE-061 median follow-up was 9 months, median OS (pembrolizumab vs chemotherapy) was 10 versus 8 months (HR, 0.64; 95% CI, 0.41-1.02), median PFS was 3 months versus 3 months (HR, 0.86; 95% CI, 0.56-1.33), ORR was 25% versus 9%, and median (range) DOR was not reached (4-26+ months) versus 7 months (3-7). In KEYNOTE-062, median follow-up was 11 months, median OS (pembrolizumab vs chemotherapy) was 17 months versus 11 months (HR, 0.69; 95% CI, 0.49-0.97), median PFS was 3 months versus 6 months (HR, 1.09, 95% CI; 0.79-1.49), ORR was 25% versus 38%, and median (range) DOR was 19 months (1+-34+) versus 7 months (2+-30+). Conclusions: This comprehensive analysis showed consistent improvements toward more favorable clinical outcomes with pembrolizumab across lines of therapy in patients with CPS{greater than or equal to}10 G/GEJ cancer.