Department of Oncology, Shanghai Chest Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, China.
Cancer Hospital Chinese Academy of Medical Sciences, Department of Medical Oncology, Beijing, China.
ESMO Open. 2024 Oct;9(10):103728. doi: 10.1016/j.esmoop.2024.103728. Epub 2024 Sep 25.
The purpose of this study was to report an updated, final analysis with longer follow-up for the open-label phase III RATIONALE-304 study of first-line tislelizumab plus chemotherapy versus chemotherapy alone for advanced nonsquamous non-small-cell lung cancer (nsq-NSCLC).
Patients with histologically confirmed stage IIIB/IV nsq-NSCLC were randomized (2 : 1) to 4-6 cycles of tislelizumab plus platinum-based chemotherapy and pemetrexed every 3 weeks, followed by maintenance tislelizumab and pemetrexed, or platinum-based chemotherapy and pemetrexed alone every 3 weeks followed by maintenance pemetrexed. The primary endpoint was independent review committee (IRC)-assessed progression-free survival (PFS). Overall survival (OS), safety, and tolerability were secondary endpoints.
Overall, 334 patients were randomized (tislelizumab plus chemotherapy: n = 223; chemotherapy: n = 111). At final analysis (median follow-up 16.1 months), safety/tolerability profiles in both arms were consistent with the interim analysis. Tislelizumab plus chemotherapy continued to demonstrate prolongation of PFS versus chemotherapy alone {stratified hazard ratio (HR) 0.63 [95% confidence interval (CI) 0.47-0.86]; median PFS 9.8 months (95% CI 8.9-11.7 months) versus 7.6 months (95% CI 5.6-8.0 months), respectively}. OS stratified HR for tislelizumab plus chemotherapy versus chemotherapy was 0.90 (95% CI 0.63-1.28), with median OS of 21.4 months (95% CI 17.7 months-not estimable) versus 21.3 months (95% CI 15.6 months-not estimable), respectively. At a subsequent ad hoc analysis (median follow-up 19.3 months), OS HR between arms was 0.85 (95% CI 0.63-1.14); when adjusted for crossover using the two-stage method, the OS HR was 0.68 (95% CI 0.48-0.96).
After longer follow-up, first-line tislelizumab plus chemotherapy continued to demonstrate a manageable safety profile and a favorable PFS benefit over chemotherapy alone in patients with advanced/metastatic nsq-NSCLC.
本研究旨在报告 RATIONALE-304 研究开放标签 III 期部分的最新、最终分析结果，该研究比较了一线替雷利珠单抗联合化疗与单纯化疗治疗晚期非鳞状非小细胞肺癌（nsq-NSCLC）的疗效。
经组织学证实为 IIIB/IV 期 nsq-NSCLC 的患者按 2:1 随机分配，接受 4-6 周期替雷利珠单抗联合铂类化疗和培美曲塞每 3 周 1 次，随后给予替雷利珠单抗和培美曲塞维持治疗，或单纯接受铂类化疗和培美曲塞每 3 周 1 次，随后给予培美曲塞维持治疗。主要终点为独立评审委员会（IRC）评估的无进展生存期（PFS）。总生存期（OS）、安全性和耐受性为次要终点。
共有 334 例患者被随机分配（替雷利珠单抗联合化疗组：n=223；化疗组：n=111）。在最终分析时（中位随访 16.1 个月），两治疗组的安全性/耐受性特征与中期分析一致。与单纯化疗相比，替雷利珠单抗联合化疗继续延长 PFS，[分层风险比（HR）0.63（95%置信区间（CI）0.47-0.86）；中位 PFS 9.8 个月（95%CI 8.9-11.7 个月）与 7.6 个月（95%CI 5.6-8.0 个月）]。替雷利珠单抗联合化疗组的 OS 分层 HR 为 0.90（95%CI 0.63-1.28），中位 OS 为 21.4 个月（95%CI 17.7 个月-无法估计）与 21.3 个月（95%CI 15.6 个月-无法估计）。在随后的一项特别分析（中位随访 19.3 个月）中，两组间 OS HR 为 0.85（95%CI 0.63-1.14）；使用两阶段法调整交叉后，OS HR 为 0.68（95%CI 0.48-0.96）。
在更长时间的随访后，与单纯化疗相比，一线替雷利珠单抗联合化疗在晚期/转移性非鳞状非小细胞肺癌患者中继续显示出可控的安全性和有利的 PFS 获益。
