Benmelstobart, anlotinib and chemotherapy in extensive-stage small-cell lung cancer: a randomized phase 3 trial

被引：50

作者：

Cheng, Ying ^{[1
]}

Chen, Jianhua ^{[2
]}

Zhang, Wei ^{[3
]}

Xie, Chao ^{[4
]}

Hu, Qun ^{[5
]}

Zhou, Ningning ^{[6
]}

Huang, Chun ^{[7
]}

Wei, Shihong ^{[8
]}

Sun, Hong ^{[9
]}

Li, Xingya ^{[10
]}

Yu, Yan ^{[11
]}

Lai, Jinhuo ^{[12
]}

Yang, Huaping ^{[13
]}

Fang, Haohui ^{[14
]}

Chen, Hualin ^{[15
]}

Zhang, Peng ^{[16
]}

Gu, Kangsheng ^{[17
]}

Wang, Qiming ^{[18
]}

Shi, Jianhua ^{[19
]}

Yi, Tienan ^{[20
]}

Xu, Xingxiang ^{[21
]}

Ye, Xianwei ^{[22
]}

Wang, Daqing ^{[23
]}

Xie, Conghua ^{[24
]}

Liu, Chunling ^{[25
]}

Zheng, Yulong ^{[26
]}

Lin, Daren ^{[27
]}

Zhuang, Wu ^{[28
]}

Lu, Ping ^{[29
]}

Yu, Guohua ^{[30
]}

Li, Jinzhang ^{[31
]}

Gu, Yuhai ^{[32
]}

Li, Baolan ^{[33
]}

Wu, Rong ^{[34
]}

Jiang, Ou ^{[35
]}

Wang, Zaiyi ^{[36
]}

Wu, Guowu ^{[37
]}

Lin, Haifeng ^{[38
]}

Zhong, Diansheng ^{[39
]}

Xu, Yanhua ^{[40
]}

Shu, Yongqian ^{[41
]}

Wu, Di ^{[42
]}

Chen, Xingwu ^{[43
]}

Wang, Jie ^{[44
]}

Wang, Minghui ^{[45
]}

Yang, Runxiang ^{[46
]}

机构：

[1] Jilin Canc Hosp, Changchun, Peoples R China

[2] Hunan Canc Hosp, Changsha, Peoples R China

[3] Nanchang Univ, Affiliated Hosp 1, Nanchang, Peoples R China

[4] Shandong Univ, Shandong Canc Hosp & Inst, Jinan, Peoples R China

[5] Inner Mongolia Univ, Affiliated Hosp, Hohhot, Peoples R China

[6] Sun Yat Sen Univ, Canc Ctr, Guangzhou, Peoples R China

[7] Tianjin Med Univ, Canc Inst & Hosp, Tianjin, Peoples R China

[8] Gansu Prov Canc Hosp, Lanzhou, Peoples R China

[9] Xi An Jiao Tong Univ, Affiliated Hosp 1, Xian, Peoples R China

[10] Zhengzhou Univ, Affiliated Hosp 1, Zhengzhou, Peoples R China

[11] Harbin Med Univ, Canc Hosp, Harbin, Peoples R China

[12] Fujian Med Univ, Union Hosp, Fuzhou, Peoples R China

[13] Cent South Univ, Xiangya Hosp, Changsha, Peoples R China

[14] Anhui Chest Hosp, Hefei, Peoples R China

[15] Guangdong Med Univ, Affiliated Hosp, Zhanjiang, Peoples R China

[16] Shanghai Pulm Hosp, Shanghai, Peoples R China

[17] Anhui Med Univ, Affiliated Hosp 1, Hefei, Peoples R China

[18] Zhengzhou Univ, Henan Canc Hosp, Affiliated Canc Hosp, Zhengzhou, Peoples R China

[19] Linyi Canc Hosp, Linyi, Peoples R China

[20] Xiangyang Cent Hosp, Xiangyang, Peoples R China

[21] Northern Jiangsu Peoples Hosp, Yangzhou, Peoples R China

[22] Guizhou Prov Peoples Hosp, Guiyang, Peoples R China

[23] Hengshui Peoples Hosp, Hengshui, Peoples R China

[24] Wuhan Univ, Zhongnan Hosp, Wuhan, Peoples R China

[25] Xinjiang Med Univ, Canc Hosp, Urumqi, Peoples R China

[26] Zhejiang Univ, Sch Med, Affiliated Hosp 1, Hangzhou, Peoples R China

[27] Jiangmen Cent Hosp, Jiangmen, Peoples R China

[28] Fujian Canc Hosp, Fuzhou, Peoples R China

[29] Xinxiang Med Coll, Affiliated Hosp 1, Xinxiang, Peoples R China

[30] Weifang Peoples Hosp, Weifang, Peoples R China

[31] Qinghai Univ, Affiliated Hosp, Xining, Peoples R China

[32] Qinghai Prov Peoples Hosp, Xining, Peoples R China

[33] Capital Med Univ, Beijing Chest Hosp, Beijing, Peoples R China

[34] China Med Univ, Shengjing Hosp, Shenyang, Peoples R China

[35] Second Peoples Hosp Neijiang, Neijiang, Peoples R China

[36] Xinjiang Med Univ, Affiliated Hosp 1, Urumqi, Peoples R China

[37] Meizhou Peoples Hosp, Meizhou, Peoples R China

[38] Hainan Med Univ, Affiliated Hosp 2, Haikou, Peoples R China

[39] Tianjin Med Univ, Gen Hosp, Tianjin, Peoples R China

[40] Jingzhou Cent Hosp, Jingzhou, Peoples R China

[41] Jiangsu Prov Hosp, Nanjing, Peoples R China

[42] Shenzhen Peoples Hosp, Shenzhen, Peoples R China

[43] Wannan Med Coll, Affiliated Hosp 1, Wuhu, Peoples R China

[44] Chinese Acad Med Sci, Canc Hosp, Beijing, Peoples R China

[45] Sun Yat Sen Univ, Sun Yat Sen Mem Hosp, Guangzhou, Peoples R China

[46] Yunnan Canc Hosp, Kunming, Peoples R China

来源：

NATURE MEDICINE | 2024年 / 30卷 / 10期

关键词：

COMBINATION; SURVIVAL; EFFICACY; CRITERIA; TQB2450; IB;

D O I：

10.1038/s41591-024-03132-1

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：

Immunochemotherapy is the first-line standard for extensive-stage small-cell lung cancer (ES-SCLC). Combining the regimen with anti-angiogenesis may improve efficacy. ETER701 was a multicenter, double-blind, randomized, placebo-controlled phase 3 trial that investigated the efficacy and safety of benmelstobart (a novel programmed death-ligand 1 (PD-L1) inhibitor) with anlotinib (a multi-target anti-angiogenic small molecule) and standard chemotherapy in treatment-naive ES-SCLC. The ETER701 trial assessed two primary endpoints: Independent Review Committee-assessed progression-free survival per RECIST 1.1 and overall survival (OS). Here the prespecified final progression-free survival and interim OS analysis is reported. Patients randomly received benmelstobart and anlotinib plus etoposide/carboplatin (EC; n = 246), placebo and anlotinib plus EC (n = 245) or double placebo plus EC ('EC alone'; n = 247), followed by matching maintenance therapy. Compared with EC alone, median OS was prolonged with benmelstobart and anlotinib plus EC (19.3 versus 11.9 months; hazard ratio 0.61; P = 0.0002), while improvement of OS was not statistically significant with anlotinib plus EC (13.3 versus 11.9 months; hazard ratio 0.86; P = 0.1723). The incidence of grade 3 or higher treatment-related adverse events was 93.1%, 94.3% and 87.0% in the benmelstobart and anlotinib plus EC, anlotinib plus EC, and EC alone groups, respectively. This study of immunochemotherapy plus multi-target anti-angiogenesis as first-line treatment achieved a median OS greater than recorded in prior randomized studies in patients with ES-SCLC. The safety profile was assessed as tolerable and manageable. Our findings suggest that the addition of anti-angiogenesis therapy to immunochemotherapy may represent an efficacious and safe approach to the management of ES-SCLC. ClinicalTrials.gov identifier: NCT04234607. In this triple-arm, placebo-controlled phase 3 trial, first-line treatment of patients with extensive-stage small-cell lung cancer with the anti-PD-L1 benmelstobart, tyrosine kinase inhibitor anlotinib and chemotherapy (CT) showed improved survival outcomes compared with anlotinib and CT or CT alone.

引用

页码：1819 / 1822

页数：19

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