# 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

## TL;DR

Adding pembrolizumab to chemotherapy improved survival and response in Japanese patients with advanced esophageal cancer, with manageable side effects over a year of follow-up.

## Contribution

Extended 1-year follow-up data from Japanese patients in the KEYNOTE-590 trial, showing sustained efficacy and safety of pembrolizumab plus chemotherapy.

## Key findings

- Pembrolizumab–chemotherapy showed a trend toward better overall and progression-free survival compared to placebo–chemotherapy.
- Patients with early tumor shrinkage ≥20% had significantly better survival and progression-free outcomes.
- Grade 3–5 treatment-related adverse events were observed in 74.3% of pembrolizumab–chemotherapy patients.

## Abstract

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.

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.

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.

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.

The online version contains supplementary material available at 10.1007/s10388-024-01053-z.