Perioperative tislelizumab plus neoadjuvant chemotherapy for patients with resectable non-small-cell lung cancer: final analysis of the randomized RATIONALE-315 trial
Later report from the trial registered as NCT04379635, in Annals of Oncology (2026); its title describes an updated or longer-term analysis.
Overview
Background: Perioperative 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 perioperative 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 perioperative 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. The secondary endpoints included pathological complete response, overall survival (OS), disease-free survival, and safety.
Results: In total, 453 patients were randomized (226 to tislelizumab and 227 to placebo). At the final analysis (median study follow-up of 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}. The 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. The 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.
Clinical trial number: NCT04379635.
Indexed on Europe PMC as PubMed record 41344593 (DOI 10.1016/j.annonc.2025.11.017). Its abstract cites the registry id NCT04379635, which is how it was matched to this trial; no figure has been checked by an editor.
A second publication from the trial, later than the first and described in its title as an update or longer-term analysis. Read it with the primary publication linked from the trial page; the record was linked automatically and its figures have not been checked by hand.
- Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.
- Chosen as a later report by words in its title (updated, long-term, final, overall survival or a year count), not by reading the paper.