First-line pembrolizumab plus chemotherapy for advanced/metastatic esophageal cancer: 1-year extended follow-up in the Japanese subgroup of the phase 3 KEYNOTE-590 study

Abstract

Background: First-line pembrolizumab plus chemotherapy (pembrolizumab–chemotherapy) demonstrated improved efficacy and a manageable safety profile versus placebo plus chemotherapy (placebo–chemotherapy) in the subgroup analysis of Japanese patients with advanced/metastatic esophageal cancer in KEYNOTE-590 at a median follow-up of 24.4 months. Longer-term data from the Japanese subgroup analysis of KEYNOTE-590 are reported. Methods: Patients were randomly assigned 1:1 to pembrolizumab 200 mg or placebo every 3 weeks for ≤ 35 cycles plus chemotherapy (cisplatin 80 mg/m2 and 5-fluorouracil 800 mg/m2/day). Endpoints included overall survival (OS) and progression-free survival (PFS; investigator-assessed per RECIST v1.1; dual primary) and safety (secondary). Early tumor shrinkage (ETS) and depth of response (DpR) were assessed post hoc. Results: Overall, 141 patients were enrolled in Japan. As of July 9, 2021, median follow-up was 36.6 months (range, 29.8–45.7). Pembrolizumab–chemotherapy showed a trend toward favorable OS (hazard ratio [HR], 0.70; 95% confidence interval [CI] 0.47–1.03) and PFS (0.57; 0.39–0.83) versus placebo–chemotherapy. In the pembrolizumab–chemotherapy group, patients with ETS ≥ 20% (55/74; 74.3%) versus < 20% (19/74; 25.7%) had favorable OS (HR, 0.23; 95% CI 0.12–0.42) and PFS (0.24; 0.13–0.43). Patients with DpR ≥ 60% (31/74; 41.9%) versus < 60% (43/74; 58.1%) had favorable OS (HR, 0.37; 95% CI 0.20–0.68) and PFS (0.24; 0.13–0.43). Grade 3–5 treatment-related adverse events occurred in 55/74 patients (74.3%) with pembrolizumab–chemotherapy and 41/67 patients (61.2%) with placebo–chemotherapy. Conclusions: With longer-term follow-up of Japanese patients with advanced/metastatic esophageal cancer, efficacy continued to favor pembrolizumab–chemotherapy compared with placebo–chemotherapy, with no new safety signals observed. Clinical trial registration: ClinicalTrials.gov, NCT03189719.