Consolidative nivolumab versus observation in unresectable stage III non-small cell lung cancer patients following neoadjuvant nivolumab plus chemotherapy and concurrent chemoradiotherapy (CA209-7AL): a randomized clinical trial.

IF 52.7 1区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Signal Transduction and Targeted Therapy Pub Date : 2025-09-29 DOI:10.1038/s41392-025-02408-3

Bo Qiu,Yuanyuan Zhao,Wenzhuo He,Weijin Zeng,Hongmei Zhang,Weineng Feng,Jun Jia,Daodu Wang,Daquan Wang,Fangjie Liu,Songran Liu,Shaohan Yin,Chuanmiao Xie,Rui Zhou,Yi Hu,Qianwen Liu,Jinyu Guo,Suping Guo,Yingjia Wu,Qiaoting Luo,Jibin Li,Yunpeng Yang,Liangping Xia,Li Zhang,Hui Liu

{"title":"Consolidative nivolumab versus observation in unresectable stage III non-small cell lung cancer patients following neoadjuvant nivolumab plus chemotherapy and concurrent chemoradiotherapy (CA209-7AL): a randomized clinical trial.","authors":"Bo Qiu,Yuanyuan Zhao,Wenzhuo He,Weijin Zeng,Hongmei Zhang,Weineng Feng,Jun Jia,Daodu Wang,Daquan Wang,Fangjie Liu,Songran Liu,Shaohan Yin,Chuanmiao Xie,Rui Zhou,Yi Hu,Qianwen Liu,Jinyu Guo,Suping Guo,Yingjia Wu,Qiaoting Luo,Jibin Li,Yunpeng Yang,Liangping Xia,Li Zhang,Hui Liu","doi":"10.1038/s41392-025-02408-3","DOIUrl":null,"url":null,"abstract":"CA209-7AL is a randomized, multicenter, phase 2 trial evaluating the efficacy and safety of consolidative nivolumab (NIVO) versus observation following neoadjuvant NIVO plus chemotherapy and concurrent chemoradiotherapy (CCRT) for unresectable stage III NSCLC. Patients received 2 cycles of neoadjuvant chemo-NIVO therapy (docetaxel + cisplatin + NIVO) and CCRT (total dose 54-64 Gy). Post-CCRT, eligible patients were randomized 1:1 to receive consolidative NIVO (360 mg every 3 weeks for up to 12 months) or observation. The primary endpoint was progression-free survival (PFS) from randomization. Between December 3rd, 2019, and August 18th, 2023, 264 patients were enrolled, and 172 were randomized to NIVO consolidation (n = 86) or observation (n = 86). With a median follow-up of 22·8 months, NIVO consolidation resulted in significantly longer PFS than did observation (median not reached vs. 12.2 months [95% CI 10.2-20.8]; stratified hazard ratio 0·49 [95% CI 0.30-0.79], p = 0.003). NIVO consolidation also demonstrated superior PFS compared with a parallel real-world study, where patients received CCRT followed by consolidative immunotherapy (median PFS: 15.7 months [95% CI 11.9-NA]). Grade 3 or 4 toxicities occurred in 9.3% of patients in the consolidation group versus 4·6% in the observation group, with similar rates of pneumonitis (2.3% each) and proximal bronchial tree toxicity (3.5% vs. 2.3%). Treatment-related death occurred in 1 (1.2%) patient in the consolidation group because of pneumonitis. Patients with a high TMB had a longer PFS with consolidation (NR vs. 15.2 months, p = 0.042). Consolidative NIVO following neoadjuvant NIVO plus chemotherapy and CCRT demonstrated effectiveness and tolerability for patients with unresectable stage III NSCLC (ClinicalTrials.gov NCT04085250).","PeriodicalId":21766,"journal":{"name":"Signal Transduction and Targeted Therapy","volume":"66 1","pages":"317"},"PeriodicalIF":52.7000,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Signal Transduction and Targeted Therapy","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1038/s41392-025-02408-3","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

CA209-7AL is a randomized, multicenter, phase 2 trial evaluating the efficacy and safety of consolidative nivolumab (NIVO) versus observation following neoadjuvant NIVO plus chemotherapy and concurrent chemoradiotherapy (CCRT) for unresectable stage III NSCLC. Patients received 2 cycles of neoadjuvant chemo-NIVO therapy (docetaxel + cisplatin + NIVO) and CCRT (total dose 54-64 Gy). Post-CCRT, eligible patients were randomized 1:1 to receive consolidative NIVO (360 mg every 3 weeks for up to 12 months) or observation. The primary endpoint was progression-free survival (PFS) from randomization. Between December 3rd, 2019, and August 18th, 2023, 264 patients were enrolled, and 172 were randomized to NIVO consolidation (n = 86) or observation (n = 86). With a median follow-up of 22·8 months, NIVO consolidation resulted in significantly longer PFS than did observation (median not reached vs. 12.2 months [95% CI 10.2-20.8]; stratified hazard ratio 0·49 [95% CI 0.30-0.79], p = 0.003). NIVO consolidation also demonstrated superior PFS compared with a parallel real-world study, where patients received CCRT followed by consolidative immunotherapy (median PFS: 15.7 months [95% CI 11.9-NA]). Grade 3 or 4 toxicities occurred in 9.3% of patients in the consolidation group versus 4·6% in the observation group, with similar rates of pneumonitis (2.3% each) and proximal bronchial tree toxicity (3.5% vs. 2.3%). Treatment-related death occurred in 1 (1.2%) patient in the consolidation group because of pneumonitis. Patients with a high TMB had a longer PFS with consolidation (NR vs. 15.2 months, p = 0.042). Consolidative NIVO following neoadjuvant NIVO plus chemotherapy and CCRT demonstrated effectiveness and tolerability for patients with unresectable stage III NSCLC (ClinicalTrials.gov NCT04085250).

查看原文本刊更多论文

巩固性纳武单抗与观察新辅助纳武单抗加化疗和同步放化疗（CA209-7AL）后不可切除的III期非小细胞肺癌患者：一项随机临床试验

CA209-7AL是一项随机、多中心、2期试验，旨在评估巩固性尼武单抗（NIVO）与新辅助NIVO +化疗和同步放化疗（CCRT）治疗不可切除的III期NSCLC的疗效和安全性。患者接受2个周期的新辅助化疗-NIVO治疗（多西紫杉醇+顺铂+ NIVO）和CCRT（总剂量54-64 Gy）。ccrt后，符合条件的患者按1:1随机分配，接受巩固NIVO（每3周360 mg，持续12个月）或观察。主要终点是随机化后的无进展生存期（PFS）。2019年12月3日至2023年8月18日，纳入264例患者，其中172例随机分为NIVO巩固组（n = 86）和观察组（n = 86）。中位随访时间为22.8个月，NIVO巩固导致的PFS明显长于观察组（中位未达到vs. 12.2个月[95% CI 10.2-20.8]；分层风险比0.49 [95% CI 0.30-0.79], p = 0.003）。与一项平行的现实世界研究相比，NIVO巩固也显示出更高的PFS，其中患者接受CCRT后进行巩固性免疫治疗（中位PFS: 15.7个月[95% CI 11.9-NA]）。巩固组3级或4级毒性发生率为9.3%，而观察组为4.6%，肺炎（各2.3%）和近端支气管树毒性发生率相似（3.5%对2.3%）。巩固组中有1例（1.2%）患者因肺炎导致治疗相关死亡。TMB高的患者有更长的PFS与巩固（NR比15.2个月，p = 0.042）。新辅助NIVO +化疗和CCRT后的巩固NIVO对不可切除的III期NSCLC患者显示出有效性和耐受性（ClinicalTrials.gov NCT04085250）。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Signal Transduction and Targeted Therapy Biochemistry, Genetics and Molecular Biology-Genetics

CiteScore

44.50

自引率

1.50%

发文量

384

审稿时长

5 weeks

期刊介绍： Signal Transduction and Targeted Therapy is an open access journal that focuses on timely publication of cutting-edge discoveries and advancements in basic science and clinical research related to signal transduction and targeted therapy. Scope: The journal covers research on major human diseases, including, but not limited to: Cancer,Cardiovascular diseases,Autoimmune diseases,Nervous system diseases.