Tislelizumab (PD-1) + CAPOX vs CAPOX/FOLFOX Chemo Backbone Shows No Clear PFS/ORR Win in 1L HER2− GC/GEJ (MAIC)

Tislelizumab is an anti–PD-1 monoclonal antibody combined here with fluoropyrimidine/platinum chemotherapy (CAPOX or FOLFOX) for first-line unresectable/metastatic HER2-negative gastric/gastroesophageal junction adenocarcinoma. In an exploratory, unanchored matching-adjusted indirect comparison (MAIC) weighting individual patient data from RATIONALE-305 (tislelizumab+CAPOX) to match aggregate DisTinGuish Part C (tislelizumab+CAPOX or tislelizumab+FOLFOX), the mixed-backbone group had numerically longer median PFS (10.5 vs 7.2 months; HR 1.24, 95% CI 0.93-1.65; p=0.1423) with no statistically significant ORR difference (56.5% vs 48.8%; OR 0.71, 95% CI 0.44-1.15; p=0.1675). With today’s PD-1+chemo first-line SOC (e.g., nivolumab+FOLFOX/CAPOX in CheckMate 649; ORR ~60% vs 45% with chemo alone), these MAIC results don’t show a clear efficacy differentiator between CAPOX-only and CAPOX/FOLFOX backbones—and they also can’t substitute for randomized head-to-head data given residual confounding risk in unanchored MAICs (RATIONALE-305: NCT03777657; DisTinGuish: NCT04363801).