Tislelizumab (anti–PD-1) + chemo extends OS to 17.2mo in 1L advanced ESCC with 3-year durability

Tislelizumab is an anti–PD-1 monoclonal antibody designed to limit Fcγ receptor binding on macrophages, here combined with investigator-selected platinum-based chemotherapy as first-line treatment for unresectable advanced/metastatic esophageal squamous cell carcinoma (ESCC) in the randomized Phase 3 RATIONALE-306 trial (NCT03783442). With a minimum follow-up of 36 months (n=649), tislelizumab + chemotherapy maintained a significant overall survival advantage over placebo + chemotherapy, with median OS of 17.2 versus 10.6 months (HR 0.70; 95% CI 0.59–0.83). At three years, 22.1% versus 14.1% of patients were alive, and progression-free survival rates were 15.0% versus 2.9%, respectively. Median time to deterioration in physical functioning was not reached with tislelizumab versus 18.8 months with chemotherapy alone, with no new safety signals identified. For context, other first-line PD-1 combinations, including pembrolizumab + chemotherapy in KEYNOTE-590, have independently demonstrated survival benefits in advanced ESCC. However, differences in patient populations, chemotherapy backbones, and subsequent treatments prevent reliable cross-trial comparisons of relative efficacy. Tislelizumab + platinum-containing chemotherapy is already FDA-approved for first-line unresectable or metastatic ESCC with PD-L1 expression ≥1; this longer-term publication strengthens the durability evidence for an established treatment rather than introducing a new option.