Investigating the Synergistic Effects of Pembrolizumab and Chemotherapy in Gastric and Gastroesophageal Junction Cancer.

Purpose: Although immune checkpoint inhibitors (ICIs) and chemotherapy combinations have been approved for the treatment of gastric and gastroesophageal junction cancer (GC/GEJC), whether immunochemotherapy (ICT) offers advantages over the simple addition of individual monotherapies remains unclear. This study aimed to investigate whether ICT has a synergistic effect in patients with advanced GC/GEJC.

Materials and methods: Reconstructed individual patient data were electronically extracted from the Kaplan-Meier curves of 3 randomized controlled trials comparing pembrolizumab (KEYNOTE-061, KEYNOTE-062, and KEYNOTE-859). The observed progression-free survival (PFS) curve for each monotherapy was used to estimate the simulated PFS curve expected under an independent drug action model. If the observed curve demonstrated significantly better PFS than the simulated curve, combined ICI and chemotherapy was determined to have a synergistic effect, implying a superior outcome compared to adding-component monotherapy.

Results: In patients with programmed cell death ligand 1 combined positive scores of ≥1 (n=2,194), the 1-year and median PFS of the observed and simulated curves were 28.0% vs. 27.9% and 6.89 months vs. 6.88 months, respectively. The one-sample log-rank test revealed no significant differences between the observed and simulated curves (P=0.107).

Conclusions: The observed PFS with ICT was comparable to the predicted PFS based on the data for each monotherapy. Our findings do not provide direct evidence of synergistic effects, but they suggest that combining ICI and chemotherapy does not compromise efficacy. These results may support the continued clinical use of ICT in patients with advanced GC/GEJC.