Tislelizumab 联合化疗作为局部晚期或转移性非鳞状非小细胞肺癌的一线治疗（RATIONALE-304：随机 III 期试验的最终分析）。

IF 7.1 2区医学 Q1 ONCOLOGY ESMO Open Pub Date : 2024-10-01 DOI:10.1016/j.esmoop.2024.103728

S. Lu , J. Wang , Y. Yu , X. Yu , Y. Hu , Z. Ma , X. Li , W. He , Y. Bao , M. Wang

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引用次数: 0

摘要

研究背景本研究的目的是报告开放标签III期RATIONALE-304研究的最新最终分析结果和更长的随访时间，该研究的目的是对晚期非鳞状非小细胞肺癌（nsq-NSCLC）一线替舒瑞单抗联合化疗与单独化疗进行对比：组织学确诊的IIIB/IV期nsq-NSCLC患者被随机分配（2:1）至4-6个周期的替舒利珠单抗+铂类化疗和培美曲塞，每3周1次，然后维持替舒利珠单抗和培美曲塞；或铂类化疗和培美曲塞，每3周1次，然后维持培美曲塞。主要终点是独立审查委员会（IRC）评估的无进展生存期（PFSIRC）。总生存期（OS）、安全性和耐受性是次要终点：共有 334 名患者接受了随机治疗（替莱珠单抗加化疗：223 人；化疗：111 人）。在最终分析中（中位随访16.1个月），两组患者的安全性/耐受性情况与中期分析结果一致。Tislelizumab联合化疗与单独化疗相比，PFSIRC继续延长{分层危险比（HR）0.63[95%置信区间（CI）0.47-0.86]；中位PFSIRC分别为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）}。tislelizumab联合化疗与化疗的OS分层HR为0.90（95% CI 0.63-1.28），中位OS分别为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）。在随后的临时分析中（中位随访19.3个月），两组间的OS HR为0.85（95% CI 0.63-1.14）；如果使用两阶段法对交叉进行调整，OS HR为0.68（95% CI 0.48-0.96）：结论：经过更长时间的随访，一线替赛珠单抗联合化疗在晚期/转移性nsq-NSCLC患者中继续显示出可控的安全性，并且与单用化疗相比，PFS获益更多。

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Tislelizumab plus chemotherapy as first-line treatment of locally advanced or metastatic nonsquamous non-small-cell lung cancer (final analysis of RATIONALE-304: a randomized phase III trial)

Background

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).

Materials and methods

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_IRC). Overall survival (OS), safety, and tolerability were secondary endpoints.

Results

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_IRC versus chemotherapy alone {stratified hazard ratio (HR) 0.63 [95% confidence interval (CI) 0.47-0.86]; median PFS_IRC 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).

Conclusions

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.

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来源期刊

ESMO Open Medicine-Oncology

CiteScore

11.70

自引率

2.70%

发文量

255

审稿时长

10 weeks

期刊介绍： ESMO Open is the online-only, open access journal of the European Society for Medical Oncology (ESMO). It is a peer-reviewed publication dedicated to sharing high-quality medical research and educational materials from various fields of oncology. The journal specifically focuses on showcasing innovative clinical and translational cancer research. ESMO Open aims to publish a wide range of research articles covering all aspects of oncology, including experimental studies, translational research, diagnostic advancements, and therapeutic approaches. The content of the journal includes original research articles, insightful reviews, thought-provoking editorials, and correspondence. Moreover, the journal warmly welcomes the submission of phase I trials and meta-analyses. It also showcases reviews from significant ESMO conferences and meetings, as well as publishes important position statements on behalf of ESMO. Overall, ESMO Open offers a platform for scientists, clinicians, and researchers in the field of oncology to share their valuable insights and contribute to advancing the understanding and treatment of cancer. The journal serves as a source of up-to-date information and fosters collaboration within the oncology community.