Peri-operative tislelizumab plus neoadjuvant chemotherapy for patients with resectable non-small cell lung cancer: final analysis of the randomized RATIONALE-315 trial
Mené sur 453 patients atteints d'un cancer du poumon non à petites cellules de stade II-IIIA et résécable (durée médiane de suivi : 38,5 mois), cet essai randomisé de phase III évalue l'efficacité, du point de vue de la survie sans événement, et la toxicité de l'ajout périopératoire du tislélizumab à une chimiothérapie néoadjuvante
Background: Peri-operative immunotherapy, particularly anti-programmed cell death protein-1 therapy, combined with neoadjuvant chemotherapy has emerged as one of the standard-of-care options for resectable non-small cell lung cancer (NSCLC). We report the final analysis of RATIONALE-315, a randomized, double-blind, phase III trial evaluating the efficacy and safety of peri-operative tislelizumab plus neoadjuvant chemotherapy versus neoadjuvant chemotherapy alone in patients with resectable, stage II-IIIA NSCLC.
Patients and methods: Adult patients in China were randomized (1:1) to receive either peri-operative tislelizumab or placebo in combination with neoadjuvant chemotherapy. The dual primary endpoints were event-free survival (EFS) and major pathological response, assessed by blinded independent central review. Secondary endpoints included pathological complete response, overall survival (OS), disease-free survival, and safety.
Results: In total, 453 patients were randomized (226 to tislelizumab, 227 to placebo). At the final analysis (median study follow-up 38.5 months), patients in the tislelizumab group experienced statistically significantly improved OS versus those in the placebo group [hazard ratio (HR) 0.65 (95% confidence interval [CI] 0.45-0.93); P = 0.009]. Median OS was not reached in either group. The 36-month OS rate was 79.3% in the tislelizumab group versus 69.3% in the placebo group. Median EFS was not reached in the tislelizumab group versus 30.6 months in the placebo group [HR 0.58 (95% CI 0.43-0.79)]. Survival benefits were generally consistent across subgroups. The safety profile of tislelizumab plus chemotherapy was tolerable and consistent with known profiles of the individual therapies.
Conclusions: Neoadjuvant tislelizumab plus chemotherapy and adjuvant tislelizumab demonstrated a statistically significant, clinically meaningful OS benefit and sustained, clinically meaningful EFS improvement compared with neoadjuvant chemotherapy, with a tolerable safety profile in patients with resectable stage II-IIIA NSCLC. These results support the use of this regimen in this patient population.
Annals of Oncology , résumé, 2025