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

Tianshu Liu,Jianming Xu,Lin Shen,Ye Hua,Jin Li,Junning Cao,Yuxian Bai,Liwei Wang,Weiguo Su,Rui-Hua Xu,Hongming Pan,Songhua Fan,Dongsheng Zhang

doi:10.1186/s13045-016-0384-9

Abstract

BackgroundTo assess the efficacy and safety of fruquintinib, a vascular endothelial growth factor receptor (VEGFR) inhibitor, in metastatic colorectal cancer (mCRC) patients.MethodsA 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).ResultsIn 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.ConclusionsFruquintinib 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 registrationNCT01975077 and NCT02196688

Highlights

To assess the efficacy and safety of fruquintinib, a vascular endothelial growth factor receptor (VEGFR) inhibitor, in metastatic colorectal cancer patients
In patients with metastatic colorectal cancer, addition of anti-vascular endothelial growth factor (VEGF) and anti-endothelial growth factor receptor (EGFR) biologic agents to chemotherapy regimens, either in the first or second line, improves overall survival (OS), progression-free survival (PFS), and anti-tumor response compared with chemotherapy alone [1,2,3]
We report here data on a phase Ib expansion trial (NCT01975077) and a randomized, double-blind, placebo-controlled, multicenter phase II trial (NCT02196688) to further assess the safety and efficacy of fruquintinib at the RP2D in patients with metastatic colorectal cancer (mCRC) who failed at least two prior standard treatments

Summary

Introduction

To assess the efficacy and safety of fruquintinib, a vascular endothelial growth factor receptor (VEGFR) inhibitor, in metastatic colorectal cancer (mCRC) patients. In patients with metastatic colorectal cancer (mCRC), addition of anti-vascular endothelial growth factor (VEGF) and anti-endothelial growth factor receptor (EGFR) biologic agents to chemotherapy regimens, either in the first or second line, improves overall survival (OS), progression-free survival (PFS), and anti-tumor response compared with chemotherapy alone [1,2,3]. The VEGF and vascular epidermal growth factor receptor (VEGFR) signaling pathways strongly promote tumor growth and metastasis. Inhibition of these pathways has demonstrated strong clinical anti-tumor activity against multiple types of cancer, leading to the successful approval of both monoclonal antibody drugs and small molecule VEGFR inhibitors [6,7,8].

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