Journal Article

Fruquintinib plus paclitaxel versus placebo plus paclitaxel for gastric or gastroesophageal junction adenocarcinoma: the randomized phase 3 FRUTIGA trial

Gu, Kangsheng, Chen, Donghui, Shu, Yongqian, Cheng, Ying, Tang, Yong, Li, Wei, Pan, Hongming, Yin, Xianli, Chen, Zhendong, Li, Guoxin, Li, Man, Li, Qiu, Qin, Yanru, Liu, Tianshu, Mao, Weidong, Wang, Shubin, Deng, Yanhong, Yuan, Ying, Zhou, Fuxiang, Liu, Qiqi, Su, Weiguo, Dai, Wenxiang, Hu, Wenwei, Zhang, Tao, Ma, Dong, Bai, Yuxian, Shi, Michael, Xu, Rui-Hua, Fan, Songhua, Pan, Yueyin, Zhao, Fuyou, Guo, Weijian, Wang, Feng, Shen, Lin, Ye, Feng, Yang, Lei, Qin, Shukui, Wang, Jufeng, Li, Jin, Zhong, Haijun, Tan, Panfeng

2024

Overview

The vascular endothelial growth factor pathway plays a key role in the pathogenesis of gastric cancer. In the multicenter, double-blind phase 3 FRUTIGA trial, 703 patients with advanced gastric or gastroesophageal junction adenocarcinoma who progressed on fluorouracil- and platinum-containing chemotherapy were randomized (1:1) to receive fruquintinib (an inhibitor of vascular endothelial growth factor receptor-1/2/3; 4 mg orally, once daily) or placebo for 3 weeks, followed by 1 week off, plus paclitaxel (80 mg/m 2 intravenously on days 1/8/15 per cycle). The study results were positive as one of the dual primary endpoints, progression-free survival (PFS), was met (median PFS, 5.6 months in the fruquintinib arm versus 2.7 months in the placebo arm; hazard ratio 0.57; 95% confidence interval 0.48–0.68; P  < 0.0001). The other dual primary endpoint, overall survival (OS), was not met (median OS, 9.6 months versus 8.4 months; hazard ratio 0.96, 95% confidence interval 0.81–1.13; P  = 0.6064). The most common grade ≥3 adverse events were neutropenia, leukopenia and anemia. Fruquintinib plus paclitaxel as a second-line treatment significantly improved PFS, but not OS, in Chinese patients with advanced gastric or gastroesophageal junction adenocarcinoma and could potentially be another treatment option for these patients. ClinicalTrials.gov registration: NCT03223376 . In a randomized, double-blind, placebo-controlled phase 3 trial, the anti-vascular endothelial growth factor receptor small-molecule inhibitor fruquintinib plus chemotherapy significantly extended progression-free survival, but not overall survival, as second-line therapy in patients with advanced gastric or gastroesophageal junction cancers.

• Publisher: Nature Publishing Group US,Nature Publishing Group
• Subject: 5-Fluorouracil / 631/67/1059/153 / 692/308/153 / 692/699/67/1504/1829 / 692/700/565/1436/1437 / Adenocarcinoma / Adenocarcinoma - drug therapy / Adenocarcinoma - pathology / Adult / Aged / Aged, 80 and over / Anemia / Antineoplastic Combined Chemotherapy Protocols - adverse effects / Antineoplastic Combined Chemotherapy Protocols - therapeutic use / Benzofurans - administration & dosage / Benzofurans - adverse effects / Benzofurans - therapeutic use / Biomedical and Life Sciences / Biomedicine / Cancer / Cancer Research / Chemotherapy / Double-Blind Method / Esophageal Neoplasms - drug therapy / Esophageal Neoplasms - pathology / Esophagogastric Junction - drug effects / Esophagogastric Junction - pathology / Female / Gastric cancer / Growth factors / Humans / Infectious Diseases / Inhibitors / Leukopenia / Male / Metabolic Diseases / Middle Aged / Molecular Medicine / Neurosciences / Neutropenia / Paclitaxel / Paclitaxel - administration & dosage / Paclitaxel - adverse effects / Paclitaxel - therapeutic use / Pathogenesis / Placebos / Progression-Free Survival / Quinazolines - administration & dosage / Quinazolines - adverse effects / Quinazolines - therapeutic use / Quinolines - administration & dosage / Quinolines - adverse effects / Quinolines - therapeutic use / Receptors / Stomach Neoplasms - drug therapy / Stomach Neoplasms - pathology / Survival / Vascular endothelial growth factor / Vascular endothelial growth factor receptors