替雷利珠单抗（Tislelizumab）与多西他赛在经治的晚期非小细胞肺癌患者中的比较(Rationale-303)

SCI

29 Octember 2022

Tislelizumab Versus Docetaxel in Patients With Previously Treated Advanced NSCLC (RATIONALE-303): A Phase 3, Open-Label, Randomized Controlled Trial

（J Thorac Oncol；IF:20.121）

Zhou C, Huang D, Fan Y, et al. Tislelizumab Versus Docetaxel in Patients With Previously Treated Advanced NSCLC (RATIONALE-303): A Phase 3, Open-Label, Randomized Controlled Trial [published online ahead of print, 2022 Sep 29]. J Thorac Oncol. 2022 

CORRESPONDENCE TO : caicunzhoudr@163.com

Introduction 引言

The phase 3 RATIONALE-303 trial (NCT03358875) investigated the efficacy and safety of tislelizumab versus docetaxel in pretreated patients with advanced NSCLC. Here, we report the efficacy and safety results and describe the exploratory biomarker analyses.

三期临床试验Rationalale-303 (NCT03358875)研究了替雷利珠单抗与多西他赛在经治的晚期非小细胞肺癌(NSCLC)患者中的疗效和安全性。在这里，我们报告了疗效和安全性结果，并描述了探索性生物标志物分析。

Methods 方法

A total of 805 patients aged more than or equal to 18 years with locally advanced or metastatic squamous or nonsquamous NSCLC were randomized 2:1 to intravenous tislelizumab 200 mg or docetaxel 75 mg/m2 every 3 weeks. Coprimary end points were overall survival (OS) in the intent-to-treat (ITT) and programmed death-ligand 1 (PD-L1) tumor cell expression greater than or equal to 25% populations. The exploratory biomarker analyses included PD-L1 expression, tumor mutation burden, and gene expression profile.

805例18岁及以上的局部晚期或转移的鳞状或非鳞状非小细胞肺癌患者被随机分为2：1静脉注射替利珠单抗200 mg或多西紫杉醇75 mg/m2，每3周一次。主要终点是意向性治疗（ITT）以及PD-L1表达高于25%的人群中的总生存（OS）。探索性生物标志物分析包括PD-L1表达、肿瘤突变负荷(TMB)和基因表达谱。

Results 结果

At the prespecified interim analysis (August 10, 2020), the co-primary end point of OS in the ITT population was met, with a statistically significant and clinically meaningful improvement in OS with tislelizumab versus docetaxel (median 17.2 versus 11.9 mo, respectively; hazard ratio [HR] = 0.64, p < 0.0001). At the final analysis (July 15, 2021), the other co-primary end point of OS in the PD-L1 tumor cell greater than or equal to 25% population was further met (median 19.3 versus 11.5 mo, respectively; HR = 0.53, p < 0.0001), and OS continued to improve in the ITT population (median 16.9 versus 11.9 mo, respectively, HR = 0.66). Exploratory biomarker analyses revealed the potential association of NOTCH1-4 mutations with improved tislelizumab efficacy for both OS and progression-free survival, whereas tissue tumor mutation burden correlated with progression-free survival benefit, but not OS benefit. No new safety signals were identified.

在预先指定的中期分析中(2020年8月10日)，ITT人群达到了OS的主要终点，对比替雷利珠单抗与多西紫杉醇，OS的改善具有统计学意义及临床意义(中位数分别为17.2个月和11.9个月；HR0.64；P<0.0001)。在最终分析中(2021年7月15日)，PD-L1 TC≥25%人群中的OS达到了主要终点 (中位数分别为19.3个月和11.5月；HR=0.53；P<0.0001)，并且在ITT人群的OS有持续改善(中位数分别为16.9个月和11.9个月；HR=0.66)。探索性生物标志物分析表明，NOTCH1-4突变可能与改善Tislelizumab对OS和PFS的疗效有关，而组织TMB与PFS益处相关，但与OS获益无关。没有发现新的安全信号。

Conclusions 结论

Tislelizumab was found to have a significantly improved and long-term clinical benefit in OS versus docetaxel in pretreated patients with advanced NSCLC, regardless of PD-L1 expression.

无论PD-L1表达如何，Tislelizumab在接受经治的晚期NSCLC患者中，与多西紫杉醇相比，在OS方面显示出显著的改善和长期临床获益。