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. The RATIONALE-306 trial demonstrated improved overall survival in participants with advanced/metastatic esophageal squamous cell carcinoma treated with tislelizumab plus chemotherapy comparing with those who received placebo plus chemotherapy. Here they report its exploratory long-term efficacy/safety/quality of life analysis after 36.0 months follow-up.