First-line cadonilimab plus chemotherapy in HER2-negative advanced gastric or gastroesophageal junction adenocarcinoma: a randomized, double-blind, phase 3 trial

被引:1
|
作者
Shen, Lin [1 ]
Zhang, Yanqiao [2 ]
Li, Ziyu [3 ]
Zhang, Xiaotian [1 ]
Gao, Xiangyu [1 ]
Liu, Bo [4 ]
Wang, Yusheng [5 ]
Ba, Yi [6 ]
Li, Ning [7 ]
Zhang, Ruixing [8 ]
Zhang, Jingdong [9 ]
Chen, Ye [10 ]
Chen, Jian [11 ]
Huang, Mingzhu [12 ]
Fu, Yang [13 ]
Liu, Mulin [14 ]
Liu, Zheng [15 ]
Zhao, Jun [16 ]
Li, Wei [17 ]
Wei, Jia [18 ]
Li, Changzheng [4 ]
Xu, Nong [19 ]
Guo, Zengqing [20 ]
Cao, Bangwei [21 ]
Liu, Lian [22 ]
Nie, Peng [23 ]
Wan, Lixin [24 ]
Sheng, Lili [25 ]
Liu, Zhenyang [26 ]
He, Yifu [27 ]
Gu, Kangsheng [28 ]
Wu, Guowu [29 ]
Wang, Weibo [30 ]
Zhang, Futong [31 ]
Qiu, Wensheng [32 ]
Guo, Jun [33 ]
Ying, Jieer [34 ]
Pan, Hongming [35 ]
Xu, Huiting [36 ]
Yuan, Yuan [37 ]
Bai, Yuansong [38 ]
Wang, Zhenghua [39 ]
Xu, Jiye [40 ]
Zhao, Xuehong [41 ]
Liu, Hao [42 ]
Zhang, Xizhi [43 ]
Dai, Wenxiang [44 ]
Xu, Hongyan [45 ]
Liu, Ming [46 ]
Xie, Lin [47 ]
机构
[1] Peking Univ, State Key Lab Holist Integrat Management Gastroint, Beijing Key Lab Carcinogenesis & Translat Res, Canc Hosp & Inst, Beijing, Peoples R China
[2] Harbin Med Univ, Canc Hosp, Harbin, Peoples R China
[3] Peking Univ, Gastrointestinal Canc Ctr, Key Lab Carcinogenesis & Translat Res, Minist Educ Beijing,Canc Hosp & Inst, Beijing, Peoples R China
[4] Shandong Canc Hosp, Dept Gastroenterol, Jinan, Peoples R China
[5] Shanxi Prov Canc Hosp, Taiyuan, Peoples R China
[6] Tianjin Med Univ, Canc Inst & Hosp, Tianjin, Peoples R China
[7] Henan Canc Hosp, Zhengzhou, Peoples R China
[8] Hebei Med Univ, Hosp 4, Shijiazhuang, Peoples R China
[9] Liaoning Canc Hosp & Inst, Shenyang, Peoples R China
[10] Henan Univ Sci & Technol, Affiliated Hosp 1, Luoyang, Peoples R China
[11] Yantai Yuhuangding Hosp, Yantai, Peoples R China
[12] Fudan Univ, Shanghai Canc Ctr, Shanghai, Peoples R China
[13] Zhengzhou Univ, Affiliated Hosp 1, Zhengzhou, Peoples R China
[14] Bengbu Med Univ, Affiliated Hosp 1, Bengbu, Peoples R China
[15] HanDan Cent Hosp, Handan, Peoples R China
[16] Changzhi Peoples Hosp, Changzhi, Peoples R China
[17] Jilin Univ, Bethune Hosp 1, Changchun, Peoples R China
[18] Nanjing Drum Tower Hosp, Nanjing, Peoples R China
[19] Zhejiang Univ, Sch Med, Affiliated Hosp 1, Hangzhou, Peoples R China
[20] Fujian Canc Hosp, Fuzhou, Peoples R China
[21] Capital Med Univ, Beijing Friendship Hosp, Beijing, Peoples R China
[22] Shandong Univ, Qilu Hosp, Jinan, Peoples R China
[23] Gansu Wuwei Tumour Hosp, Wuwei, Peoples R China
[24] Nanyang Cent Hosp, Nanyang, Peoples R China
[25] Wannan Med Coll, Affiliated Hosp 1, Wuhu, Peoples R China
[26] Hunan Canc Hosp, Changsha, Peoples R China
[27] Anhui Prov Canc Hosp, Hefei, Peoples R China
[28] Anhui Med Univ, Affiliated Hosp 1, Hefei, Peoples R China
[29] Meizhou Peoples Hosp, Meizhou, Peoples R China
[30] Shandong Prov Hosp, Jinan, Peoples R China
[31] Shijiazhuang Peoples Hosp, Shijiazhuang, Peoples R China
[32] Qingdao Univ, Affiliated Hosp, Qingdao, Peoples R China
[33] Xingtai Peoples Hosp, Xingtai, Peoples R China
[34] Zhejiang Canc Hosp, Hangzhou, Peoples R China
[35] Zhejiang Univ, Sir Run Run Shaw Hosp, Sch Med, Hangzhou, Peoples R China
[36] Hubei Canc Hosp, Wuhan, Peoples R China
[37] Xuzhou Cent Hosp, Xuzhou, Peoples R China
[38] Jilin Univ, Bethune Hosp 3, Changchun, Peoples R China
[39] Jinzhou Med Univ, Affiliated Hosp 1, Jinzhou, Peoples R China
[40] Zhoukou Cent Hosp, Zhoukou, Peoples R China
[41] Linfen Cent Hosp, Linfen, Peoples R China
[42] Sichuan Prov Peoples Hosp, Chengdu, Peoples R China
[43] Northern Jiangsu Peoples Hosp, Yangzhou, Peoples R China
[44] Univ South China, Affiliated Hosp 1, Hengyang, Peoples R China
[45] Weihai Municipal Hosp, Weihai, Peoples R China
[46] Sichuan Univ, West China Hosp, Chengdu, Peoples R China
[47] Yunnan Canc Hosp, Kunming, Yunnan, Peoples R China
[48] Xinjiang Med Univ, Affiliated Canc Hosp, Urumqi, Peoples R China
[49] Taizhou Hosp Zhejiang Prov, Linhai, Peoples R China
[50] China Med Univ, Hosp 1, Shenyang, Peoples R China
基金
中国国家自然科学基金;
关键词
OPEN-LABEL; CANCER; IPILIMUMAB; MULTICENTER; NIVOLUMAB; COMBINATION; CARBOPLATIN; PACLITAXEL; HER2;
D O I
10.1038/s41591-024-03450-4
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Programmed cell death protein-1 (PD-1) inhibitors plus chemotherapy have been the standard of care in the first-line treatment of advanced gastric or gastroesophageal junction (G/GEJ) adenocarcinoma; however, the survival benefits are modest in patients with low programmed death ligand 1 (PD-L1) expression. Here we investigated the efficacy and safety of cadonilimab (PD-1/cytotoxic T lymphocyte antigen-4 (CTLA-4) bispecific antibody) plus chemotherapy as first-line treatment in G/GEJ adenocarcinoma. The prespecified interim analysis is reported here. This was a randomized, double-blind, placebo-controlled phase 3 study. Eligible patients were adults with untreated, unresectable, locally advanced or metastatic G/GEJ adenocarcinoma. Patients were randomized 1:1 to receive cadonilimab (10 mg kg(-1) every 3 weeks) or placebo plus chemotherapy (every 3 weeks). The primary endpoint was overall survival (OS) in the intention-to-treat population (one-sided significance level, P = 0.025). Secondary endpoints included OS in patients with a PD-L1 combined positive score >= 5, progression-free survival, objective response rate, duration of response and safety. As of 18 August 2023, 610 patients from 75 study centers were randomized to cadonilimab (n = 305) or placebo (n = 305). With a median follow-up of 18.7 months, the cadonilimab group had a significantly longer median OS (14.1 versus 11.1 months; hazard ratio (HR) 0.66; 95% confidence interval (CI) 0.54-0.81; P < 0.001) than the placebo group. The primary endpoint was met. The median progression-free survival was 7.0 months versus 5.3 months (HR 0.53, 95% CI 0.44-0.65). The median OS in patients with a PD-L1 combined positive score >= 5 was 15.3 months versus 10.9 months (HR 0.58, 95% CI 0.41-0.82). The objective response rate was 65.2% versus 48.9% with a median duration of response of 8.8 months versus 4.4 months. Grade >= 3 treatment-related adverse events occurred in 65.9% of the cadonilimab group and 53.6% of the placebo group, and the most common were decreased platelet count, decreased neutrophil count and anemia. Most of the immune-related adverse events were grade 1 or 2. No new safety signals were observed. Cadonilimab plus chemotherapy significantly improved OS with a manageable safety profile in patients with advanced G/GEJ adenocarcinoma.
引用
收藏
页码:1163 / 1170
页数:23
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