针对可切除非小细胞肺癌患者的围手术期替莱利珠单抗加新辅助化疗（RATIONALE-315）：随机临床试验的中期分析

IF 38.7 1区医学 Q1 CRITICAL CARE MEDICINE

Lancet Respiratory Medicine Pub Date : 2024-11-21 DOI:10.1016/s2213-2600(24)00269-8

Dongsheng Yue, Wenxiang Wang, Hongxu Liu, Qixun Chen, Chun Chen, Lunxu Liu, Peng Zhang, Guofang Zhao, Fan Yang, Guang Han, Ying Cheng, Bentong Yu, Yue Yang, Haiquan Chen, Jie Jiang, Lijie Tan, Shidong Xu, Naiquan Mao, Jian Hu, Lanjun Zhang, Xibin Zhuang

{"title":"针对可切除非小细胞肺癌患者的围手术期替莱利珠单抗加新辅助化疗（RATIONALE-315）：随机临床试验的中期分析","authors":"Dongsheng Yue, Wenxiang Wang, Hongxu Liu, Qixun Chen, Chun Chen, Lunxu Liu, Peng Zhang, Guofang Zhao, Fan Yang, Guang Han, Ying Cheng, Bentong Yu, Yue Yang, Haiquan Chen, Jie Jiang, Lijie Tan, Shidong Xu, Naiquan Mao, Jian Hu, Lanjun Zhang, Xibin Zhuang","doi":"10.1016/s2213-2600(24)00269-8","DOIUrl":null,"url":null,"abstract":"<h3>Background</h3>Treatment guidelines recommend neoadjuvant or adjuvant chemotherapy, with or without immune checkpoint inhibitors, for resectable non-small-cell lung cancer (NSCLC). We report the interim results for the phase 3 RATIONALE-315 study, which aimed to investigate perioperative tislelizumab for the treatment of resectable NSCLC.<h3>Methods</h3>RATIONALE-315 is a randomised, double-blind, placebo-controlled phase 3 trial conducted at 50 sites (hospitals or academic research centres) in China. Patients (aged ≥18 years) with untreated stage II–IIIA squamous or non-squamous NSCLC were randomly assigned (1:1) to neoadjuvant tislelizumab 200 mg or placebo intravenously every 3 weeks, plus platinum-based doublet chemotherapy followed by surgery and adjuvant tislelizumab 400 mg or placebo every 6 weeks. Dual primary endpoints were major pathological response rate and event-free survival, analysed by intention to treat. Safety was also assessed in all patients who received at least one dose of study treatment. RATIONALE-315 is registered with <span><span>ClinicalTrials.gov</span><svg aria-label=\"Opens in new window\" focusable=\"false\" height=\"20\" viewbox=\"0 0 8 8\"><path d=\"M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z\"></path></svg></span>, <span><span>NCT04379635</span><svg aria-label=\"Opens in new window\" focusable=\"false\" height=\"20\" viewbox=\"0 0 8 8\"><path d=\"M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z\"></path></svg></span>, and is active but not recruiting.<h3>Findings</h3>Between June 8, 2020, and Aug 31, 2022, 453 patients were assigned to tislelizumab (n=226) or placebo (n=227). The median age of patients was 62·0 years (IQR 56·0–67·0). 410 (91%) of 453 patients were male and 43 (9%) were female. As of Aug 21, 2023 (data cutoff for the interim analysis of event-free survival), median duration of follow-up was 22·0 months (IQR 15·5–28·0). Tislelizumab significantly improved event-free survival versus placebo (stratified hazard ratio 0·56 [95% CI 0·40–0·79]; one-sided p=0·0003). The major pathological response rate was significantly higher in the tislelizumab group (56% [95% CI 50–63]) than in the placebo group (15% [11–20]; difference 41% [33–49]; one-sided p<0·0001). Grade 3 or worse adverse events and serious treatment-related adverse events occurred in 163 (72%) of 226 patients and 35 (15%) of 226 patients, respectively, in the tislelizumab group, and in 150 (66%) and 18 (8%) patients, respectively, in the placebo group. The most common grade 3 or worse treatment-related adverse event was decreased neutrophil count (138 [61%] of 226 in the tislelizumab group <em>vs</em> 134 [59%] of 226 in the placebo group). 31 (14%) of 226 patients in the tislelizumab group and 45 (20%) of 227 patients in the placebo group died during the study.<h3>Interpretation</h3>Perioperative tislelizumab plus neoadjuvant chemotherapy showed a clinically meaningful and statistically significant improvement in efficacy and a manageable safety profile compared with neoadjuvant chemotherapy in patients with resectable stage II–IIIA NSCLC.<h3>Funding</h3>BeiGene.","PeriodicalId":51307,"journal":{"name":"Lancet Respiratory Medicine","volume":"23 1","pages":""},"PeriodicalIF":38.7000,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Perioperative tislelizumab plus neoadjuvant chemotherapy for patients with resectable non-small-cell lung cancer (RATIONALE-315): an interim analysis of a randomised clinical trial\",\"authors\":\"Dongsheng Yue, Wenxiang Wang, Hongxu Liu, Qixun Chen, Chun Chen, Lunxu Liu, Peng Zhang, Guofang Zhao, Fan Yang, Guang Han, Ying Cheng, Bentong Yu, Yue Yang, Haiquan Chen, Jie Jiang, Lijie Tan, Shidong Xu, Naiquan Mao, Jian Hu, Lanjun Zhang, Xibin Zhuang\",\"doi\":\"10.1016/s2213-2600(24)00269-8\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<h3>Background</h3>Treatment guidelines recommend neoadjuvant or adjuvant chemotherapy, with or without immune checkpoint inhibitors, for resectable non-small-cell lung cancer (NSCLC). We report the interim results for the phase 3 RATIONALE-315 study, which aimed to investigate perioperative tislelizumab for the treatment of resectable NSCLC.<h3>Methods</h3>RATIONALE-315 is a randomised, double-blind, placebo-controlled phase 3 trial conducted at 50 sites (hospitals or academic research centres) in China. Patients (aged ≥18 years) with untreated stage II–IIIA squamous or non-squamous NSCLC were randomly assigned (1:1) to neoadjuvant tislelizumab 200 mg or placebo intravenously every 3 weeks, plus platinum-based doublet chemotherapy followed by surgery and adjuvant tislelizumab 400 mg or placebo every 6 weeks. Dual primary endpoints were major pathological response rate and event-free survival, analysed by intention to treat. Safety was also assessed in all patients who received at least one dose of study treatment. RATIONALE-315 is registered with <span><span>ClinicalTrials.gov</span><svg aria-label=\\\"Opens in new window\\\" focusable=\\\"false\\\" height=\\\"20\\\" viewbox=\\\"0 0 8 8\\\"><path d=\\\"M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z\\\"></path></svg></span>, <span><span>NCT04379635</span><svg aria-label=\\\"Opens in new window\\\" focusable=\\\"false\\\" height=\\\"20\\\" viewbox=\\\"0 0 8 8\\\"><path d=\\\"M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z\\\"></path></svg></span>, and is active but not recruiting.<h3>Findings</h3>Between June 8, 2020, and Aug 31, 2022, 453 patients were assigned to tislelizumab (n=226) or placebo (n=227). The median age of patients was 62·0 years (IQR 56·0–67·0). 410 (91%) of 453 patients were male and 43 (9%) were female. As of Aug 21, 2023 (data cutoff for the interim analysis of event-free survival), median duration of follow-up was 22·0 months (IQR 15·5–28·0). Tislelizumab significantly improved event-free survival versus placebo (stratified hazard ratio 0·56 [95% CI 0·40–0·79]; one-sided p=0·0003). The major pathological response rate was significantly higher in the tislelizumab group (56% [95% CI 50–63]) than in the placebo group (15% [11–20]; difference 41% [33–49]; one-sided p<0·0001). Grade 3 or worse adverse events and serious treatment-related adverse events occurred in 163 (72%) of 226 patients and 35 (15%) of 226 patients, respectively, in the tislelizumab group, and in 150 (66%) and 18 (8%) patients, respectively, in the placebo group. The most common grade 3 or worse treatment-related adverse event was decreased neutrophil count (138 [61%] of 226 in the tislelizumab group <em>vs</em> 134 [59%] of 226 in the placebo group). 31 (14%) of 226 patients in the tislelizumab group and 45 (20%) of 227 patients in the placebo group died during the study.<h3>Interpretation</h3>Perioperative tislelizumab plus neoadjuvant chemotherapy showed a clinically meaningful and statistically significant improvement in efficacy and a manageable safety profile compared with neoadjuvant chemotherapy in patients with resectable stage II–IIIA NSCLC.<h3>Funding</h3>BeiGene.\",\"PeriodicalId\":51307,\"journal\":{\"name\":\"Lancet Respiratory Medicine\",\"volume\":\"23 1\",\"pages\":\"\"},\"PeriodicalIF\":38.7000,\"publicationDate\":\"2024-11-21\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Lancet Respiratory Medicine\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1016/s2213-2600(24)00269-8\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CRITICAL CARE MEDICINE\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Lancet Respiratory Medicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/s2213-2600(24)00269-8","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CRITICAL CARE MEDICINE","Score":null,"Total":0}

引用次数: 0

摘要

背景治疗指南建议对可切除的非小细胞肺癌（NSCLC）进行新辅助或辅助化疗，同时使用或不使用免疫检查点抑制剂。我们报告了3期RATIONALE-315研究的中期结果，该研究旨在探讨围手术期使用替赛珠单抗治疗可切除的NSCLC。未经治疗的II-IIIA期鳞状或非鳞状NSCLC患者（年龄≥18岁）被随机分配（1:1）到新辅助治疗中，每3周静脉注射替斯利珠单抗200毫克或安慰剂，外加铂类双联化疗，然后进行手术和辅助治疗，每6周静脉注射替斯利珠单抗400毫克或安慰剂。双主要终点是主要病理反应率和无事件生存期，按意向治疗进行分析。此外，还对所有至少接受过一次治疗的患者进行了安全性评估。研究结果2020年6月8日至2022年8月31日期间，453名患者被分配到替斯利珠单抗（226人）或安慰剂（227人）治疗。患者的中位年龄为62-0岁（IQR 56-0-67-0）。453名患者中有410名（91%）为男性，43名（9%）为女性。截至2023年8月21日（无事件生存期中期分析的数据截止日期），中位随访时间为22-0个月（IQR为15-5-28-0）。与安慰剂相比，Tislelizumab能显著改善无事件生存期（分层危险比为0-56 [95% CI 0-40-0-79]; 单侧p=0-0003）。替斯利珠单抗组的主要病理反应率（56% [95% CI 50-63]）明显高于安慰剂组（15% [11-20]；差异 41% [33-49]；单侧 p<0-0001）。3级或更严重的不良事件和严重的治疗相关不良事件分别发生在替舒利珠单抗组226例患者中的163例（72%）和安慰剂组226例患者中的35例（15%），以及替舒利珠单抗组150例（66%）和安慰剂组18例（8%）患者中。最常见的 3 级或更严重的治疗相关不良事件是中性粒细胞计数减少（替莱珠单抗组 226 例患者中有 138 例[61%]，安慰剂组 226 例患者中有 134 例[59%]）。tislelizumab组226名患者中有31人（14%）在研究期间死亡，安慰剂组227名患者中有45人（20%）在研究期间死亡。解释在可切除的II-IIIA期NSCLC患者中，围手术期tislelizumab联合新辅助化疗与新辅助化疗相比，疗效有临床意义，统计学上有显著改善，安全性可控。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

查看原文本刊更多论文

Perioperative tislelizumab plus neoadjuvant chemotherapy for patients with resectable non-small-cell lung cancer (RATIONALE-315): an interim analysis of a randomised clinical trial

Background

Treatment guidelines recommend neoadjuvant or adjuvant chemotherapy, with or without immune checkpoint inhibitors, for resectable non-small-cell lung cancer (NSCLC). We report the interim results for the phase 3 RATIONALE-315 study, which aimed to investigate perioperative tislelizumab for the treatment of resectable NSCLC.

Methods

RATIONALE-315 is a randomised, double-blind, placebo-controlled phase 3 trial conducted at 50 sites (hospitals or academic research centres) in China. Patients (aged ≥18 years) with untreated stage II–IIIA squamous or non-squamous NSCLC were randomly assigned (1:1) to neoadjuvant tislelizumab 200 mg or placebo intravenously every 3 weeks, plus platinum-based doublet chemotherapy followed by surgery and adjuvant tislelizumab 400 mg or placebo every 6 weeks. Dual primary endpoints were major pathological response rate and event-free survival, analysed by intention to treat. Safety was also assessed in all patients who received at least one dose of study treatment. RATIONALE-315 is registered with ClinicalTrials.gov, NCT04379635, and is active but not recruiting.

Findings

Between June 8, 2020, and Aug 31, 2022, 453 patients were assigned to tislelizumab (n=226) or placebo (n=227). The median age of patients was 62·0 years (IQR 56·0–67·0). 410 (91%) of 453 patients were male and 43 (9%) were female. As of Aug 21, 2023 (data cutoff for the interim analysis of event-free survival), median duration of follow-up was 22·0 months (IQR 15·5–28·0). Tislelizumab significantly improved event-free survival versus placebo (stratified hazard ratio 0·56 [95% CI 0·40–0·79]; one-sided p=0·0003). The major pathological response rate was significantly higher in the tislelizumab group (56% [95% CI 50–63]) than in the placebo group (15% [11–20]; difference 41% [33–49]; one-sided p<0·0001). Grade 3 or worse adverse events and serious treatment-related adverse events occurred in 163 (72%) of 226 patients and 35 (15%) of 226 patients, respectively, in the tislelizumab group, and in 150 (66%) and 18 (8%) patients, respectively, in the placebo group. The most common grade 3 or worse treatment-related adverse event was decreased neutrophil count (138 [61%] of 226 in the tislelizumab group vs 134 [59%] of 226 in the placebo group). 31 (14%) of 226 patients in the tislelizumab group and 45 (20%) of 227 patients in the placebo group died during the study.

Interpretation

Perioperative tislelizumab plus neoadjuvant chemotherapy showed a clinically meaningful and statistically significant improvement in efficacy and a manageable safety profile compared with neoadjuvant chemotherapy in patients with resectable stage II–IIIA NSCLC.

Funding

BeiGene.

求助全文

通过发布文献求助，成功后即可免费获取论文全文。去求助

来源期刊

Lancet Respiratory Medicine RESPIRATORY SYSTEM-RESPIRATORY SYSTEM

CiteScore

87.10

自引率

0.70%

发文量

572

期刊介绍： The Lancet Respiratory Medicine is a renowned journal specializing in respiratory medicine and critical care. Our publication features original research that aims to advocate for change or shed light on clinical practices in the field. Additionally, we provide informative reviews on various topics related to respiratory medicine and critical care, ensuring a comprehensive coverage of the subject. The journal covers a wide range of topics including but not limited to asthma, acute respiratory distress syndrome (ARDS), chronic obstructive pulmonary disease (COPD), tobacco control, intensive care medicine, lung cancer, cystic fibrosis, pneumonia, sarcoidosis, sepsis, mesothelioma, sleep medicine, thoracic and reconstructive surgery, tuberculosis, palliative medicine, influenza, pulmonary hypertension, pulmonary vascular disease, and respiratory infections. By encompassing such a broad spectrum of subjects, we strive to address the diverse needs and interests of our readership.