Mefatinib versus gefitinib as a first-line treatment for EGFR-mutated non-small cell lung cancer: a randomized, double-blind, multicenter phase III study
Abstract
Mefatinib, a novel second-generation epidermal growth factor (EGFR) tyrosine kinase inhibitor that has shown promising antitumor activity in targeting non-small cell lung cancer (NSCLC) with common and uncommon EGFR- activating mutations. In this phase III, randomized, double-blind trial in China, 336 eligible patients with advanced nonsquamous NSCLC harboring EGFR L858R or exon 19 deletion (ex19del) were assigned (2:1) to receive either mefatinib (60 mg daily, n = 223) or gefitinib (250 mg daily, n = 113). The primary endpoint was progression-free survival (PFS), assessed by an independent review committee (IRC). The trial is registered with chinadrugtrials.org.cn (CTR20192297). After a median follow-up of 15.9 months for mefatinib and 18.5 months for gefitinib, mefatinib demonstrated a significantly longer median IRC-assessed PFS compared to gefitinib (13.7 vs. 9.7 months; hazard ratio [HR] = 0.68; 95% confidence intervals [CI]: 0.53–0.87; p = 0.002). The 30-month overall survival rate was 60.2% for mefatinib and 54.3% for gefitinib. Patients with EGFR ex19del had comparable PFS for both treatment arms ( p > 0.100), whereas patients with EGFR L858R had significantly longer median PFS when treated with mefatinib than gefitinib (13.7 vs 8.3 months HR = 0.55 [95% CI: 0.38–0.78]; p = 0.001). Patients with EGFR L858R had a 30-month overall survival rate of 56.6% with mefatinib and 43.7% with gefitinib. Treatment-related adverse events ≥grade 3 were reported in 45.7% of the mefatinib group and 24.8% of the gefitinib group. No new safety signals were observed for mefatinib. Mefatinib demonstrated superior efficacy to gefitinib with a similar tolerability profile in the first-line treatment of EGFR -mutated advanced NSCLC.
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Authors: Jia Yu, Anwen Xiong, Qiming Wang, Jianhua Chen, Hongrui Niu, Chengzhi Zhou, Panwen Tian, Wu Zhuang, Jie Li, Jing Wang, Kangsheng Gu, Kangsheng Gu, Jinsheng Shi, Jun Guo, Yonghui Di, Dongqing Lv, Debin Sun, Liming Cao, Zhixiong Yang, Jingxun Wu, Liyun Miao, Yueyin Pan, Chong Li, Xiaohong Wu, Jie Yin, Xiang Wang, Meili Sun, Miao He, Haohui Fang, Ping Chen, Min Zhang, Xinmei Yang, Hui Zhao, Jian Feng, Xuezhen Ma, Jian Lu, Jian Lü, Xin Zhao, Zhixiang Zhuang, Xu Sun, 朱超男, Jianghua Chen, June Xu, Kai Wang, Caicun Zhou
Institutions: Hebei Medical University, Qingdao University, Sichuan University, West China Hospital of Sichuan University, Central South University, Zhejiang University, People's Hospital of Cangzhou, Affiliated Hospital of Qingdao University, Fujian Medical University, Second Affiliated Hospital of Zhejiang University, Soochow University, Yancheng Third People's Hospital, Guangzhou Medical University, Nanjing Medical University, Tongji University, Shanghai East Hospital, First Affiliated Hospital of Xiamen University, Wuxi Fourth People's Hospital, Anhui Medical University, Deyang Stomatological Hospital, Nantong University, Xuzhou Central Hospital, Guangdong Medical College, Second Affiliated Hospital of Anhui Medical University, First Affiliated Hospital of Anhui Medical University, University of Science and Technology of China, Wenzhou Medical University, Hubei Cancer Hospital, Nanjing Drum Tower Hospital, First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, Henan Provincial People's Hospital, Henan Medical University, Shanghai Pulmonary Hospital, Powerchina Huadong Engineering Corporation (China), Xingtai People's Hospital, Xiangya Hospital Central South University, Jinan Central Hospital, First Affiliated Hospital of Zhengzhou University, Henan Cancer Hospital, Second Affiliated Hospital of Soochow University, Lishui Central Hospital, Hunan Cancer Hospital, Ganzhou People's Hospital, First Affiliated Hospital of Gannan Medical University, First Hospital of Jiaxing, Fujian Provincial Cancer Hospital, Affiliated Hospital of Nantong University, Nantong Tumor Hospital, Zhejiang Provincial People's Hospital, First Affiliated Hospital of Xinxiang Medical University, Chinese General Hospital College of Nursing and Liberal Arts, Xi'an Chest Hospital, Yancheng First People's Hospital, Yancheng Second People's Hospital