Zhou Caicun, Dong Xiaorong, Chen Gongyan, Wang Zhehai, Wu Xianghua, Yao Yu, Zhang Yiping, Cheng Ying, Pan Hongming, Zhang Xiaodong, Cui Jiuwei, Wang Lifeng, Chen Xi, Li Xiaoling, Wang Ziping, Wang Qiming, He Jianxing, Wang Mengzhao, Yan Iris, Qian Li, Xu Miao, Huang Xiayu, Sun Chun, Cai Jun, Wu Qiong, Ballinger Marcus, Kaul Monika, Srivastava Minu K
Department of Oncology, Shanghai East Hospital/Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, PR China.
Cancer Center, Union Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China.
Nat Med. 2025 May 16. doi: 10.1038/s41591-025-03658-y.
After the global approval of atezolizumab plus bevacizumab and chemotherapy as first-line metastatic nonsquamous non-small-cell lung cancer (nsqNSCLC) treatment, the IMpower151 ( NCT04194203 ) trial was conducted in China to address regional differences. Chemotherapy-naive patients with metastatic nsqNSCLC (N = 305) were randomized 1:1 to receive either atezolizumab, bevacizumab, carboplatin and paclitaxel or pemetrexed (ABCPem/Pac; n = 152) or placebo plus bevacizumab, carboplatin and pemetrexed or paclitaxel (BCPem/Pac; n = 153). The primary endpoint was investigator-assessed progression-free survival (INV-PFS); secondary endpoints included subgroup analyses of INV-PFS, independent review facility-assessed PFS, overall survival, and investigator-assessed objective response rate and duration of response per RECIST v.1.1. Most patients (97%) received pemetrexed, and 53% had EGFR tumors. Median INV-PFS for ABCPem/Pac versus BCPem/Pac was 9.5 versus 7.1 months (stratified hazard ratio: 0.84; 95% confidence interval: 0.65, 1.09; P = 0.184). INV-PFS across subgroups and independent review facility-assessed PFS were consistent with INV-PFS in the intention-to-treat population. Median overall survival was 20.7 versus 18.7 months in the ABCPem/Pac versus BCPem/Pac arms, respectively (stratified hazard ratio: 0.93; 95% confidence interval: 0.67, 1.28). Confirmed objective response rate with ABCPem/Pac versus BCPem/Pac was 48% versus 50%, respectively; median duration of response was 11.3 versus 8.3 months. Adverse events of special interest for atezolizumab were observed in 68% (grades 3 and 4: 11%) and 71% (grades 3 and 4: 7%) of patients receiving ABCPem/Pac and BCPem/Pac, respectively. The most common adverse events of special interest for atezolizumab in the ABCPem/Pac and BCPem/Pac arms were hepatitis (driven by laboratory abnormalities; mostly low grade), hypothyroidism and rash. Overall, IMpower151 did not meet its primary endpoint (INV-PFS) in metastatic nsqNSCLC. ABCPem/Pac was generally well tolerated, with no new safety signals. Trial registration number: ClinicalTrials.gov, NCT02366143.
阿特珠单抗联合贝伐单抗及化疗被全球批准用于一线治疗转移性非鳞状非小细胞肺癌（nsqNSCLC）后，开展了IMpower151（NCT04194203）试验以研究中国人群的区域差异。未接受过化疗的转移性nsqNSCLC患者（N = 305）按1:1随机分组，分别接受阿特珠单抗、贝伐单抗、卡铂和紫杉醇或培美曲塞（ABCPem/Pac；n = 152），或安慰剂联合贝伐单抗、卡铂和培美曲塞或紫杉醇（BCPem/Pac；n = 153）。主要终点为研究者评估的无进展生存期（INV-PFS）；次要终点包括INV-PFS的亚组分析、独立审查机构评估的PFS、总生存期，以及研究者评估的客观缓解率和根据RECIST v.1.1标准评估的缓解持续时间。大多数患者（97%）接受了培美曲塞，53%的患者肿瘤具有EGFR。ABCPem/Pac组与BCPem/Pac组的中位INV-PFS分别为9.5个月和7.1个月（分层风险比：0.84；95%置信区间：0.65，1.09；P = 0.184）。各亚组的INV-PFS及独立审查机构评估的PFS与意向性治疗人群中的INV-PFS一致。ABCPem/Pac组与BCPem/Pac组的中位总生存期分别为20.7个月和18.7个月（分层风险比：0.93；95%置信区间：0.67，1.28）。ABCPem/Pac组与BCPem/Pac组的确认客观缓解率分别为48%和50%；中位缓解持续时间分别为11.3个月和8.3个月。接受ABCPem/Pac和BCPem/Pac治疗的患者中，分别有68%（3/4级：11%）和71%（3/4级：7%）观察到阿特珠单抗的特殊关注不良事件。ABCPem/Pac组和BCPem/Pac组中阿特珠单抗最常见的特殊关注不良事件为肝炎（由实验室异常驱动；大多为低级别）、甲状腺功能减退和皮疹。总体而言，IMpower151在转移性nsqNSCLC中未达到其主要终点（INV-PFS）。ABCPem/Pac总体耐受性良好，未发现新的安全信号。试验注册号：ClinicalTrials.gov，NCT02366143。
