Tislelizumab Plus Chemotherapy as First-Line Treatment for Locally Advanced or Metastatic Nonsquamous NSCLC (RATIONALE 304): A Randomized Phase 3 Trial

作者:Lu, Shun*; Wang, Jie; Yu, Yan; Yu, Xinmin; Hu, Yanping; Ai, Xinghao; Ma, Zhiyong; Li, Xingya; Zhuang, Wu; Liu, Yunpeng; Li, Weidong; Cui, Jiuwei; Wang, Dong; Liao, Wangjun; Zhou, Jianying; Wang, Zhehai; Sun, Yuping; Qiu, Xiusong; Gao, Jie; Bao, Yuanyuan; Liang, Liang; Wang, Mengzhao
来源:Journal of Thoracic Oncology, 2021, 16(9): 1512-1522.
DOI:10.1016/j.jtho.2021.05.005

摘要

Introduction: Tislelizumab, an anti-programmed cell death protein-1 antibody, was specifically engineered to minimize Fc gamma R macrophage binding to abrogate antibody-dependent phagocytosis. Compared with chemotherapy alone, tislelizumab plus chemotherapy may improve clinical outcomes in patients with advanced nonsquamous NSCLC (nsq-NSCLC). Methods: In this open-label phase 3 trial (RATIONALE 304; NCT03663205), patients with histologically confirmed stage IIIB or IV nsq-NSCLC were randomized (2:1) to receive either arm A: tislelizumab plus platinum (carboplatin or cisplatin) and pemetrexed every 3 weeks (Q3Ws) or arm B: platinum and pemetrexed alone Q3W during induction treatment, followed by intravenous maintenance pemetrexed Q3W. The primary end point was progression free survival (PFS) assessed by an independent review committee; clinical response and safety and tolerability were secondary end points. Results: Overall, 332 patients (n = 222 [A]; n = 110 [B]) received treatment. With a median study follow-up of 9.8 months, PFS was significantly longer with tislelizumab plus chemotherapy compared with chemotherapy alone (median PFS: 9.7 versus 7.6 mo; hazard ratio = 0.645 [95% confidence interval: 0.462-0.902], p = 0.0044). In addition, response rates were higher and response duration was longer with combination therapy versus chemotherapy alone. Hematologic adverse events (AEs) were common in both treatment arms; the most reported AEs were grades 1 to 2 in severity. The most common grade greater than or equal to 3 AEs were associated with chemotherapy and included neutropenia (44.6% [A]; 35.5% [B]) and leukopenia (21.6% [A]; 14.5% [B]). Conclusions: Addition of tislelizumab to chemotherapy resulted in significantly prolonged PFS, higher response rates, and longer response duration compared with chemotherapy alone, identifying a new potential option for first-line treatment of advanced nsq-NSCLC irrespective of disease stage. (c) 2021 International Association for the Study of Lung Cancer. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http:// creativecommons.org/licenses/by-nc-nd/4.0/).

  • 单位
    广州医学院; 郑州大学; 1; 中国医科大学; 哈尔滨医科大学; 南方医科大学; 吉林大学; 浙江大学; 中国医学科学院北京协和医院