Qiu Bo, Zhao Yuanyuan, He Wenzhuo, Zeng Weijin, Zhang Hongmei, Feng Weineng, Jia Jun, Wang Daodu, Wang Daquan, Liu Fangjie, Liu Songran, Yin Shaohan, Xie Chuanmiao, Zhou Rui, Hu Yi, Liu Qianwen, Guo Jinyu, Guo Suping, Wu Yingjia, Luo Qiaoting, Li Jibin, Yang Yunpeng, Xia Liangping, Zhang Li, Liu Hui
Department of Radiation Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China.
Department of Medical Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China.
Signal Transduct Target Ther. 2025 Sep 29;10(1):317. doi: 10.1038/s41392-025-02408-3.
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).
CA209-7AL是一项随机、多中心的2期试验，旨在评估巩固性纳武利尤单抗（NIVO）与新辅助NIVO联合化疗及同步放化疗（CCRT）后观察等待相比，用于不可切除的III期非小细胞肺癌（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（多西他赛+顺铂+NIVO）和CCRT（总剂量54-64 Gy）。CCRT后，符合条件的患者按1:1随机分组，接受巩固性NIVO治疗（每3周360 mg，最长12个月）或观察等待。主要终点是随机分组后的无进展生存期（PFS）。在2019年12月3日至2023年8月18日期间，共入组264例患者，172例被随机分配至NIVO巩固治疗组（n = 86）或观察等待组（n = 86）。中位随访22.8个月，NIVO巩固治疗组的PFS显著长于观察等待组（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）。与一项平行的真实世界研究相比，NIVO巩固治疗也显示出更好的PFS，该研究中患者接受CCRT后进行巩固性免疫治疗（中位PFS：15.7个月[95%CI 11.9-NA]）。巩固治疗组9.3%的患者发生3级或4级毒性反应，观察等待组为4.6%，肺炎发生率相似（均为2.3%），近端支气管树毒性发生率分别为3.5%和2.3%。巩固治疗组有1例（1.2%）患者因肺炎发生治疗相关死亡。肿瘤突变负荷高的患者接受巩固治疗后的PFS更长（未达到 vs. 15.2个月，p = 0.042）。新辅助NIVO联合化疗及CCRT后进行巩固性NIVO治疗，对不可切除的III期NSCLC患者显示出有效性和耐受性（ClinicalTrials.gov NCT04085250）。
