Assessment of fluoropyrimidine and platinum-based chemotherapy regimens in combination with immunotherapy for the treatment of advanced gastric or gastroesophageal junction cancer among patients in the KEYNOTE-062, KEYNOTE-859, RATIONALE-305 and KEYN

e16071 Background: Although chemotherapy combined with immunotherapy has become the first-line standard treatment for advanced gastric or gastroesophageal junction (G/GEJ) cancer, the efficacy of fluoropyrimidine and platinum-based (FP) chemotherapy combined with immunotherapy remains unclear. We analyzed the efficacy and prognosis of FP combined with immunotherapy as first-line treatment for G/GEJ cancer using data from four Phase III trials: KEYNOTE-062, KEYNOTE-859, RATIONALE-305, and KEYNOTE-811. Methods: This post hoc analysis included patients with advanced G/GEJ cancer from the phase 3 KEYNOTE-062, KEYNOTE-859, RATIONALE-305, and KEYNOTE-811 trials. KEYNOTE-062: Patients from 200 sites in 29 countries (September 18, 2015–May 26, 2017) received pembrolizumab plus FP or FP alone. Data cutoff: March 26, 2019. KEYNOTE-859: Patients from 215 sites in 33 countries (November 8, 2018–June 11, 2021) received pembrolizumab plus FP or CAPOX. Data cutoff: October 3, 2022. RATIONALE-305: Patients from 141 sites in 13 countries (December 13, 2018–February 9, 2021) received tislelizumab plus FP or CAPOX. Data cutoff: February 28, 2023. KEYNOTE-811: Patients from 192 sites in 20 countries (October 5, 2018–August 6, 2021) received pembrolizumab plus trastuzumab and FP or CAPOX. Data cutoff: March 20, 2024. Response was assessed using RECIST v1.1. The proportion of patients receiving CAPOX vs. FP was statistically analyzed. Results: KEYNOTE-062: Pembrolizumab plus FP did not significantly improve overall survival (OS) vs. FP alone (CPS ≥1: HR=0.85; CPS ≥10: HR=0.85). Progression-free survival (PFS) showed a trend toward improvement (CPS ≥1: HR=0.84; CPS ≥10: HR=0.73) but was not statistically significant. KEYNOTE-859: Pembrolizumab plus chemotherapy significantly improved OS and PFS, particularly with CAPOX. FP showed trends but no statistical significance. RATIONALE-305: Tislelizumab plus chemotherapy improved OS, especially with CAPOX. No significant benefit was observed with FP. KEYNOTE-811: Pembrolizumab plus trastuzumab and CAPOX significantly improved objective response rates (ORR) and PFS. FP showed non-significant trends in PFS and OS. Conclusions: Therefore, based on existing clinical studies, we can conclude that the CAPOX regimen is the optimal partner for first-line immunotherapy in gastric cancer and should be considered the preferred strategy, especially for HER2-negative gastric cancer. In contrast, the FP regimen should be used with caution, or preferably not at all, as nearly all studies indicate that, despite showing a trend toward improved survival, it has not reached statistical significance.