Perioperative tislelizumab plus neoadjuvant chemotherapy for patients with resectable non-small-cell lung cancer (RATIONALE-315): an interim analysis of a randomised clinical trial,The Lancet Respiratory Medicine

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Perioperative tislelizumab plus neoadjuvant chemotherapy for patients with resectable non-small-cell lung cancer (RATIONALE-315): an interim analysis of a randomised clinical trial
The Lancet Respiratory Medicine ( IF 38.7 ) Pub Date : 2024-11-21 , DOI: 10.1016/s2213-2600(24)00269-8
Dongsheng Yue, Wenxiang Wang, Hongxu Liu, Qixun Chen, Chun Chen, Lunxu Liu, Peng Zhang, Guofang Zhao, Fan Yang, Guang Han, Ying Cheng, Bentong Yu, Yue Yang, Haiquan Chen, Jie Jiang, Lijie Tan, Shidong Xu, Naiquan Mao, Jian Hu, Lanjun Zhang, Xibin Zhuang

Background

Treatment guidelines recommend neoadjuvant or adjuvant chemotherapy, with or without immune checkpoint inhibitors, for resectable non-small-cell lung cancer (NSCLC). We report the interim results for the phase 3 RATIONALE-315 study, which aimed to investigate perioperative tislelizumab for the treatment of resectable NSCLC.

Methods

RATIONALE-315 is a randomised, double-blind, placebo-controlled phase 3 trial conducted at 50 sites (hospitals or academic research centres) in China. Patients (aged ≥18 years) with untreated stage II–IIIA squamous or non-squamous NSCLC were randomly assigned (1:1) to neoadjuvant tislelizumab 200 mg or placebo intravenously every 3 weeks, plus platinum-based doublet chemotherapy followed by surgery and adjuvant tislelizumab 400 mg or placebo every 6 weeks. Dual primary endpoints were major pathological response rate and event-free survival, analysed by intention to treat. Safety was also assessed in all patients who received at least one dose of study treatment. RATIONALE-315 is registered with ClinicalTrials.gov, NCT04379635, and is active but not recruiting.

Findings

Between June 8, 2020, and Aug 31, 2022, 453 patients were assigned to tislelizumab (n=226) or placebo (n=227). The median age of patients was 62·0 years (IQR 56·0–67·0). 410 (91%) of 453 patients were male and 43 (9%) were female. As of Aug 21, 2023 (data cutoff for the interim analysis of event-free survival), median duration of follow-up was 22·0 months (IQR 15·5–28·0). Tislelizumab significantly improved event-free survival versus placebo (stratified hazard ratio 0·56 [95% CI 0·40–0·79]; one-sided p=0·0003). The major pathological response rate was significantly higher in the tislelizumab group (56% [95% CI 50–63]) than in the placebo group (15% [11–20]; difference 41% [33–49]; one-sided p<0·0001). Grade 3 or worse adverse events and serious treatment-related adverse events occurred in 163 (72%) of 226 patients and 35 (15%) of 226 patients, respectively, in the tislelizumab group, and in 150 (66%) and 18 (8%) patients, respectively, in the placebo group. The most common grade 3 or worse treatment-related adverse event was decreased neutrophil count (138 [61%] of 226 in the tislelizumab group vs 134 [59%] of 226 in the placebo group). 31 (14%) of 226 patients in the tislelizumab group and 45 (20%) of 227 patients in the placebo group died during the study.

Interpretation

Perioperative tislelizumab plus neoadjuvant chemotherapy showed a clinically meaningful and statistically significant improvement in efficacy and a manageable safety profile compared with neoadjuvant chemotherapy in patients with resectable stage II–IIIA NSCLC.

Funding

BeiGene.

更新日期：2024-11-22

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