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

Nat Med. 2024 Aug;30(8):2189-2198. doi: 10.1038/s41591-024-02989-6. Epub 2024 Jun 1.

Abstract

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/m2 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 .

Publication types

  • Randomized Controlled Trial
  • Clinical Trial, Phase III
  • Multicenter Study

MeSH terms

  • Adenocarcinoma* / drug therapy
  • Adenocarcinoma* / pathology
  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols* / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols* / therapeutic use
  • Benzofurans* / administration & dosage
  • Benzofurans* / adverse effects
  • Benzofurans* / therapeutic use
  • Double-Blind Method
  • Esophageal Neoplasms / drug therapy
  • Esophageal Neoplasms / pathology
  • Esophagogastric Junction* / drug effects
  • Esophagogastric Junction* / pathology
  • Female
  • Humans
  • Male
  • Middle Aged
  • Paclitaxel* / administration & dosage
  • Paclitaxel* / adverse effects
  • Paclitaxel* / therapeutic use
  • Progression-Free Survival
  • Quinazolines / administration & dosage
  • Quinazolines / adverse effects
  • Quinazolines / therapeutic use
  • Quinolines / administration & dosage
  • Quinolines / adverse effects
  • Quinolines / therapeutic use
  • Stomach Neoplasms* / drug therapy
  • Stomach Neoplasms* / pathology

Substances

  • Paclitaxel
  • Benzofurans
  • HMPL-013
  • Quinazolines
  • Quinolines

Supplementary concepts

  • Adenocarcinoma Of Esophagus

Associated data

  • ClinicalTrials.gov/NCT03223376