A Phase III, randomized, double-blind, placebo-controlled, multicenter study of fruquintinib in Chinese patients with advanced nonsquamous non-small-cell lung cancer - The FALUCA study.

Fruquintinib is an orally active kinase inhibitor that selectively targets the vascular endothelial growth factor (VEGF) receptor. A Phase II trial has demonstrated a significant benefit in progression-free survival (PFS) for fruquintinib-treated patients with locally advanced/metastatic nonsquamous non-small-cell lung cancer (NSCLC) who have progressed after second-line chemotherapy. This Phase III trial is a randomized, double-blind, multicenter trial to confirm fruquintinib's efficacy in the same patient population. From December 2015 to February 2018, 730 patients were screened, of whom 527 were enrolled into the study. Participants were randomized 2:1 to receive fruquintinib (n = 354) or placebo (n = 173) once daily for 3 weeks on-treatment, and 1 week off-treatment. Patients were stratified according to epidermal growth factor receptor mutation status and prior use of VEGF inhibitors. Primary endpoint was overall survival (OS). Median OS was 8.9 months for the fruquintinib group and 10.4 months for placebo group (hazard ratio [HR] 1.02; 95 % confidence interval [CI], 0.82-1.28; P = 0.841), with median PFS of 3.7 months and 1.0 months, respectively (HR 0.34; 95 % CI, 0.28-0.43; P < 0.001). Objective response rate and disease control rate were 13.8 % and 66.7 % for fruquintinib, and 0.6 % and 24.9 % for placebo, respectively (P < 0.001). Hypertension was the most frequent treatment-emergent adverse event (≥grade 3) observed in fruquintinib-treated patients (21.0 %). Post hoc analysis revealed that fruquintinib prolonged the median OS for patients who did not receive subsequent antitumor therapy: 7.0 months versus 5.1 months for placebo (HR 0.65; 95 % CI, 0.46-0.91; P = 0.012). Patients receiving fruquintinib also reported improvements in quality of life for most functional scales measured by EORTC QLQ-C30 and LC13 questionnaires. Although the study did not meet its primary endpoint, fruquintinib could be effective in combination with other agents for the treatment of patients with NSCLC who have failed second-line chemotherapy.

Informations de copyright

Copyright © 2020 Elsevier B.V. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of Competing Interest The following represents disclosure information provided by authors of this manuscript Shun Lu: Leading principal investigator (PI) of FALUCA study; received research support from AstraZeneca, Boehringer Ingelheim, Hutchison MediPharma and Roche; received speaker fees from AstraZeneca, Eli Lilly, Roche, and Sanofi; an advisor for AstraZeneca, Boehringer Ingelheim, Hutchison MediPharma and Roche. Gongyan Chen, Yuping Sun, Sanyuan Sun, Jianhua Chang, Yu Yao, Zhendong Chen, Feng Ye, Junguo Lu, Jianhua Shi, Jianxing He, Xiaoqing Liu, Yiping Zhang, Zhihua Liu, Jian Fang, Ying Cheng, Chunhong Hu, Weidong Mao, Yanping Hu, Youling Gong, Li Shan, Zhixiong Yang, Yong Song, Wei Li, Chong Bai, Buhai Wang, Rui Ma, Zhendong Zheng, Mingfang Liu, Zhijun Jie, Lejie Cao, Wangjun Liao, Hongming Pan, Dongning Huang, Yuan Chen, Jinji Yang, Shukui Qin, Shenglin Ma, Li Liang, Zhe Liu, Jianying Zhou, Min Tao, Yijiang Huang, Feng Qiu, Yunchao Huang: None. Sha Guan: Employment: Hutchison MediPharma. Mengye Peng: Employment: Hutchison MediPharma Weiguo Su: Employment: Hutchison MediPharma, Leadership: Hutchison MediPharma, Stock or other ownership: Hutchison Chi-Med, Travel, accommodations, expenses: Hutchison MediPharma.