First-line tislelizumab plus chemotherapy versus placebo plus chemotherapy in unresectable advanced/metastatic esophageal squamous cell carcinoma: minimum 3-year survival follow-up of a randomized phase 3 trial (RATIONALE-306)

RATIONALE-306 previously demonstrated improved overall survival (OS) in participants treated with tislelizumab plus chemotherapy versus those receiving placebo plus chemotherapy as first-line treatment for advanced/metastatic esophageal squamous cell carcinoma, with a minimum follow-up of approximately 15 months. Exploratory long-term efficacy, safety, and quality of life (QoL) analyses after 36.0 months' minimum follow-up are reported here. Patients (649) were randomized 1:1 to tislelizumab 200 mg or placebo with investigator-chosen chemotherapy. Tislelizumab plus chemotherapy improves OS versus placebo plus chemotherapy in all patients (17.2 versus 10.6 months; hazard ratio, 0.70; 95% confidence interval, 0.59-0.80). At 3 years, 15.0% of patients treated with tislelizumab plus chemotherapy had not progressed versus 2.9% of those receiving placebo plus chemotherapy. No new safety signals have been identified. Median time to deterioration of physical functioning-a key QoL domain-has not been reached with tislelizumab plus chemotherapy versus 18.8 months with placebo plus chemotherapy. With longer follow-up, tislelizumab plus chemotherapy demonstrates long-lasting efficacy, tolerable safety, and favorable patient-reported outcomes, making it a suitable option for this patient population. ClinicalTrials.gov: NCT03783442 .