Safety and efficacy of fruquintinib in patients with previously treated metastatic colorectal cancer: a phase Ib study and a randomized double-blind phase II study

J Hematol Oncol. 2017 Jan 19;10(1):22. doi: 10.1186/s13045-016-0384-9.


Background: To assess the efficacy and safety of fruquintinib, a vascular endothelial growth factor receptor (VEGFR) inhibitor, in metastatic colorectal cancer (mCRC) patients.

Methods: A phase Ib open-label study and phase II randomized, placebo-controlled trial compared the efficacy of fruquintinib plus best supportive care (BSC) with placebo plus BSC in mCRC patients with ≥2 lines of prior therapies. The primary endpoint was progression-free survival (PFS).

Results: In the phase Ib study, 42 patients took fruquintinib 5 mg for 3 weeks on/1 week off. The median PFS was 5.80 months, and the median overall survival (OS) was 8.88 months. In the phase II study, 71 patients were randomized (47 to fruquintinib, 24 to placebo). PFS was significantly improved with fruquintinib plus BSC (4.73 months; 95% confidence interval [CI] 2.86-5.59) versus placebo plus BSC (0.99 months; 95% CI 0.95-1.58); (hazard ratio [HR] 0.30; 95% CI 0.15-0.59; P < 0.001). The median OS was 7.72 versus 5.52 months (HR 0.71; 95% CI 0.38-1.34). The most common grade 3-4 adverse events were hypertension and hand-foot skin reaction.

Conclusions: Fruquintinib showed a significant PFS benefit of 3.7 months in patients with treatment-refractory mCRC. The safety profile was consistent with that of VEGFR tyrosine kinase inhibitors. A randomized phase III confirmatory study in mCRC is underway.

Trial registration: NCT01975077 and NCT02196688.

Keywords: Fruquintinib; Metastatic colorectal cancer; Progression-free survival; VEGFR.

Publication types

  • Clinical Trial, Phase I
  • Clinical Trial, Phase II
  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Adenocarcinoma / drug therapy
  • Adenocarcinoma / secondary*
  • Aged
  • Angiogenesis Inhibitors / adverse effects
  • Angiogenesis Inhibitors / therapeutic use*
  • Antineoplastic Agents, Immunological / adverse effects
  • Antineoplastic Agents, Immunological / therapeutic use*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Benzofurans / adverse effects
  • Benzofurans / therapeutic use*
  • Colorectal Neoplasms / drug therapy*
  • Disease-Free Survival
  • Double-Blind Method
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Molecular Targeted Therapy
  • Neoplasm Proteins / antagonists & inhibitors
  • Protein Kinase Inhibitors / adverse effects
  • Protein Kinase Inhibitors / therapeutic use*
  • Quinazolines / adverse effects
  • Quinazolines / therapeutic use*
  • Receptors, Vascular Endothelial Growth Factor / antagonists & inhibitors


  • Angiogenesis Inhibitors
  • Antineoplastic Agents, Immunological
  • Benzofurans
  • Neoplasm Proteins
  • Protein Kinase Inhibitors
  • Quinazolines
  • HMPL-013
  • Receptors, Vascular Endothelial Growth Factor

Associated data