KEYNOTE-059 cohort 2: Safety and efficacy of pembrolizumab (pembro) plus 5-fluorouracil (5-FU) and cisplatin for first-line (1L) treatment of advanced gastric cancer.

Abstract

4012 Background: Preliminary analyses from the global, multicohort, phase 2 KEYNOTE-059 (NCT02335411) study suggested that safety of pembro + 5-FU + cisplatin is manageable as 1L therapy in pts with advanced gastric or gastroesophageal junction (G/GEJ) cancer (cohort 2). We present efficacy and updated safety data from KEYNOTE-059 cohort 2. Methods: Cohort 2 enrolled pts ≥18 y with HER2 – recurrent or metastatic G/GEJ adenocarcinoma, measurable disease, no prior therapy for metastatic/advanced disease, and ECOG PS 0-1. Pts received pembro 200 mg on day 1 of each 21-day cycle + cisplatin 80 mg/m2 for 6 cycles + 5-FU 800 mg/m2 (or capecitabine 1000 mg/m2 in Japan) Q3W for up to 2 y or until disease progression, investigator/pt decision to withdrawal, or unacceptable toxicity. PD-L1+pts had expression in ≥1% tumor or stromal cells using IHC (22C3 antibody). End points were safety and tolerability (primary), ORR (RECIST v1.1, by central review), DOR, PFS, and OS (secondary). Results: Of 25 enrolled pts, 64% were men, 68% were Asian, and 64% had PD-L1+ tumors. Median age was 64 y. At data cutoff (Oct 19, 2016), median duration of follow-up was 12.2 mo (range, 1.8 to 19.6) and 84% of pts had discontinued treatment, mainly owing to clinical or radiologic disease progression (64%). ORR (CR + PR) was 60% (95% CI, 38.7-78.9) in all pts. Overall, 32% of pts had SD (95% CI, 14.9-53.5), 4% had PD (95% CI, 0.1-20.4), and 4% were not evaluable (95% CI, 0.1-20.4). ORR was 68.8% (95% CI, 41.3-89.0) in PD-L1+ pts and 37.5% (95% CI, 8.5-75.5) in PD-L1– pts. Median DOR (range) was 4.6 mo (2.6 to 14.4+) in all pts, 4.6 mo (3.2 to 14.4+) in PD-L1+ pts, and 5.4 mo (2.8 to 8.3+) in PD-L1–pts. Median PFS was 6.6 mo (95% CI, 5.9-10.6); median OS was 13.8 mo (95% CI, 7.3-not estimable). Grade 3-4 treatment-related adverse events (TRAEs) occurred in 76% of pts. TRAEs led to discontinuation in 3 pts (grade 3 stomatitis, grade 2 hypoacusis, and grade 1 creatinine increase). No TRAEs were fatal. Conclusions: Pembro + 5-FU + cisplatin showed manageable safety and encouraging antitumor activity as 1L therapy for pts with advanced G/GEJ cancer. Further exploration of pembro + 5-FU + cisplatin in this setting is warranted. Clinical trial information: NCT02335411.