Tislelizumab plus chemotherapy improves survival in extensive-stage small cell lung cancer

INTRODUCTION: In the final analysis of the randomized, phase 3 RATIONALE-312 trial (data cutoff: April 19, 2023), patients with extensive-stage SCLC (ES-SCLC) who received first-line tislelizumab plus chemotherapy experienced significant improvements in overall survival (OS; HR = 0.75 [95% CI: 0.61-0.93]; one-sided p = 0.004) and tolerable toxicity compared with placebo plus chemotherapy. We report long-term follow-up (data cutoff: December 29, 2023) data. METHODS: Adults with previously untreated ES-SCLC were randomized 1:1 to four induction cycles of intravenous tislelizumab 200 mg or placebo once every 3 weeks plus investigator's choice of chemotherapy (intravenous carboplatin or cisplatin plus etoposide), followed by tislelizumab or placebo maintenance. The primary end point was OS. RESULTS: With a median survival follow-up of 39.8 and 36.4 months in the tislelizumab (n = 227) and placebo (n = 230) arms, respectively, OS benefit in the intent-to-treat population was sustained compared with final analysis (median OS: 15.5 versus 13.5 mo, respectively; HR = 0.78; 95% CI: 0.63-0.95). Exploratory analyses found a consistent OS improvement favoring tislelizumab over placebo across programmed death-ligand 1 expression subgroups. The most frequently reported treatment-related adverse events in the tislelizumab and placebo arms were alopecia (78.4% versus 79.5%), anemia (76.7% versus 78.6%), and neutropenia (68.7% versus 70.3%). CONCLUSIONS: Long-term follow-up data from RATIONALE-312 reported that patients with ES-SCLC treated with first-line tislelizumab plus chemotherapy had clinically meaningful and sustained improvements in OS compared with placebo plus chemotherapy in the intent-to-treat and programmed death-ligand 1-assessable populations. Tislelizumab plus chemotherapy was tolerable, with no new safety signals identified. CLINICAL TRIAL INFORMATION: ClinicalTrials.gov Identifier: NCT04005716.