KEYNOTE-059 Update: Efficacy and safety of pembrolizumab alone or in combination with chemotherapy in patients with advanced gastric or gastroesophageal (G/GEJ) cancer

Abstract

Background: Prior results from the global, phase 2 KEYNOTE-059 study (NCT02335411) demonstrated manageable safety and promising antitumor activity for pembro alone and pembro +chemo in pts with G/GEJ cancer. Methods: Pts with recurrent or metastatic G/GEJ adenocarcinoma were enrolled. Pts were enrolled in cohorts 1 and 2 regardless of tumor PD-L1 expression; only pts with PD-L1-positive tumors (combined positive score of≥1% using the PD-L1 IHC 22C3 pharmDx assay) were enrolled in cohort 3. Cohort 1 pts received pembro alone after ≥2 prior lines of therapy. Cohort 2 pts received pembro+ cisplatin (80 mg/m2 day 1) +5-fluorouracil (800 mg/m2 days 1-5 Q3W) or capecitabine (in Japan only, 1000 mg/ m2 twice daily) as first-line. Cohort 3 pts received pembro alone as first-line. In all cohorts, pembro was given at 200 mg Q3W for up to 2 years. Primary end points were safety (all) and ORR by RECIST v1.1 by central review (cohorts 1 and 3); key secondary end points were ORR (cohort 2) and DOR by RECIST v1.1, PFS, and OS. Results: At data cutoff (Apr 21, 2017), median (range) follow-up was 6 (1-25), 14 (2- 24), and 18 (2-21) months for cohorts 1 (259 pts), 2 (25 pts) and 3 (31 pts), respectively. Confirmed ORR (95% CI) was 12% (8-17) overall, 16% (11-23) in PD-L1-positive, and 6% (3-13) in PD-L1-negative tumors in cohort 1. Confirmed ORR was 60% (39- 79) overall, 73% (45-92) in PD-L1-positive, and 38% (9-76) in PD-L1-negative tumors in cohort 2. In cohort 3, confirmed ORR (95% CI) was 26% (12-45). Median PFS (95% CI) was 2 (2-2), 7 (6-11), and 3 (2-6) months in cohorts 1, 2, and 3, respectively. Median OS (95% CI) in months was 6 (4-7), 14 (9-not estimable), and not reached (9- 21) in cohorts 1, 2, and 3, respectively. In cohorts 1, 2 and 3, grade 3-5 treatment-related adverse event (TRAE) incidence was 46 (18%), 19 (76%), and 7 (23%), respectively. In cohort 1, TRAEs led to discontinuation in 7 pts (3%) and death in 2 pts (1%); in cohort 2, TRAEs led to discontinuation in 3 pts (12%); in cohort 3, TRAEs led to death in 1 pt (3%). Conclusions: These updated results show manageable safety and promising antitumor activity for pembro alone and pembro + chemo in pts with advanced G/GEJ cancer.