Perioperative tislelizumab plus neoadjuvant chemotherapy for patients with resectable non-small-cell lung cancer: final analysis of the randomized RATIONALE-315 trial.

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.

我们报告了RATIONALE-315的最终分析结果，这是一项随机、双盲、III期试验，评估了围手术期替西利尤单抗联合新辅助化疗与仅使用新辅助化疗在可切除的II-IIIA期NSCLC患者中的疗效和安全性。

patients_and_methods

Adult patients in China were randomized (1 : 1) to receive either perioperative tislelizumab or placebo in combination with neoadjuvant chemotherapy.

中国成年患者按1:1的比例随机接受围手术期替雷利珠单抗或安慰剂联合新辅助化疗。

The dual primary endpoints were event-free survival (EFS) and major pathological response, assessed by blinded independent central review.

双重主要终点是无事件生存（EFS）和主要病理反应，通过盲法独立中央审查进行评估。

The secondary endpoints included pathological complete response, overall survival(OS), disease-free survival, and safety.

次要终点包括病理完全缓解、总生存（OS）、无病生存和安全性。

Results

In total, 453 patients were randomized (226 to tislelizumab and 227 to placebo).

总共453名患者被随机分配（226名接受替雷利珠单抗治疗，227名接受安慰剂）。

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}.

在最终分析时（中位研究随访时间为38.5个月），与安慰剂组相比，替雷利珠单抗组患者的总生存期显著改善（风险比[HR]为0.65，95%置信区间[CI]为0.45-0.93；P = 0.009）。

The median OS was not reached in either group.

两组患者的中位总生存期均未达到。

The 36-month OS rate was 79.3% in the tislelizumab group versus 69.3% in the placebo group.

在替雷利珠单抗组中，36个月的总生存率为79.3%，而在安慰剂组中为69.3%。

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)].

在替雷利珠单抗组中，无进展生存期（EFS）的中位数尚未达到，而在安慰剂组中为30.6个月[风险比（HR）0.58，95%置信区间（CI）0.43-0.79]。

Survival benefits were generally consistent across subgroups.

生存益处在各个亚组中通常保持一致。

The safety profile of tislelizumab plus chemotherapy was tolerable and consistent with known profiles of the individual therapies.

替雷利珠单抗联合化疗的安全性是可耐受的，并且与已知的各个单一疗法的特性一致。

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.

新辅助替雷利珠单抗联合化疗以及辅助替雷利珠单抗在可切除II-IIIA期非小细胞肺癌患者中显示出统计学上显著的、临床意义上的总生存期（OS）获益以及持续的、临床意义上的无进展生存期（EFS）改善，与新辅助化疗相比，具有可接受的安全性特征。

These results support the use of this regimen in this patient population.

这些结果支持在这一患者群体中使用这一治疗方案。

clinical_trial_number

NCT04379635.

NCT04379635。