Abstract

BackgroundThe multicohort, phase II, nonrandomized KEYNOTE-059 study evaluated pembrolizumabchemotherapy in advanced gastric/gastroesophageal junction cancer. Results from cohorts 2 and 3, evaluating first-line therapy, are presented.MethodsPatients 18years old had previously untreated recurrent or metastatic gastric/gastroesophageal junction adenocarcinoma. Cohort 3 (monotherapy) had programmed death receptor 1 combined positive score 1. Cohort 2 (combination therapy) received pembrolizumab 200mg on day 1, cisplatin 80mg/m(2) on day 1 (up to 6 cycles), and 5-fluorouracil 800mg/m(2) on days 1-5 of each 3-week cycle (or capecitabine 1000mg/m(2) twice daily in Japan). Primary end points were safety (combination therapy) and objective response rate per Response Evaluation Criteria in Solid Tumors version 1.1 by central review, and safety (monotherapy).ResultsIn the combination therapy and monotherapy cohorts, 25 and 31 patients were enrolled; median follow-up was 13.8months (range 1.8-24.1) and 17.5months (range 1.7-20.7), respectively. In the combination therapy cohort, grade 3/4 treatment-related adverse events occurred in 19 patients (76.0%); none were fatal. In the monotherapy cohort, grade 3-5 treatment-related adverse events occurred in seven patients (22.6%); one death was attributed to a treatment-related adverse event (pneumonitis). The objective response rate was 60.0% [95% confidence interval (CI), 38.7-78.9] (combination therapy) and 25.8% (95% CI 11.9-44.6) (monotherapy).ConclusionsPembrolizumab demonstrated antitumor activity and was well tolerated as monotherapy and in combination with chemotherapy in patients with previously untreated advanced gastric/gastroesophageal junction adenocarcinoma.Clinical Trial ClinicalTrials.gov NCT02335411