FDA Approval Sought for Fruquintinib in Refractory Metastatic Colorectal Cancer Treatment


Soon, the FDA will be considering fruquintinib for approval to treat patients with refractory metastatic colorectal cancer.

A rolling submission of a new drug application (NDA) has been completed for fruquintinib (HMPL-013) for the treatment of patients with refractory metastatic colorectal cancer (mCRC).1

Fruquintinib is a selective inhibitor of VEGFR-1, -2, and -3. The drug has been shown to inhibit the migration, proliferation, and survival of endothelial cells as well as inhibit microvessel formation, tumor cell proliferation, and tumor cell death.2 The NDA for fruquintinib is supported by data from the FRESCO-2 study (NCT04322539), in which the agent reduced the risk of death by 34% in patients with refractory mCRC.3

“This FDA submission is a significant milestone for patients in the [United States]. with metastatic CRC, one of the most common and deadly cancers in the [United States] and worldwide. Fruquintinib is an important treatment option for patients with metastatic CRC in China, where it has been available to patients since 2018. We look forward to working with our partner Takeda to commercialize fruquintinib outside China, and we remain on track to submit regulatory filings in Europe and Japan later this year,” said Michael Shi, MD, head of research and development, chief medical officer of HUTCHMED, in a press release.

Image Credit: © Dr_Microbe [stock.adobe.com]

Image Credit: © Dr_Microbe [stock.adobe.com]

FRESCO-2 was a randomized, double-blind, placebo-controlled, phase 3 study that included 691 patients with refractory mCRC from the United States, Europe, Japan, and Australia. All patients enrolled has received prior chemotherapy, and anti-VEGF therapy. In the case of RAS wild-type, patients received prior anti-EGFR therapy. Those with BRAF V600E-mutant or microsatellite instability- high disease had received ≥ 1 targeted regimen; as well as prior trifluridine/tipiracil (Lonsurf) and/or regorafenib (Stivarga) exposure. These patients were assessed for the primary end point of overall survival (OS) and the secondary end points of progression-free survival (PFS), objective response rate (ORR), disease control rate, and safety.3

Patients in the study were given fruquintinib in combination with best supportive care (BSC) or placebo and BSC. Oral fruquintinib was dosed at 5 mg once daily on a 3 weeks on and 1 week off basis in 28-day cycles, as was placebo. The median duration of treatment in the study was 11.3 months in the fruquintinib arm and 11.2 months in the placebo arm.

The median OS with fruquintinib and BSC was 7.4 months vs 4.8 months with placebo and BSC, representing a significant improvement (HR, 0.66; 95% CI, 0.55-0.80; P < .0001). The median PFS observed with fruquintinib/BSC was 3.7 months compared with 1.8 months in the placebo/BSC arm (HR, 0.32; 95% CI, 0.27-0.39; P < .001). In terms of the other efficacy end points, fruquintinib showed an ORR of 1.5% vs 0% with placebo, and the DCR was 55.5% vs 16.1%, respectively.

In the fruquintinib arm, 62.7% of patients experienced grade 3 or higher adverse events (AEs) compared with 50.4% of the placebo arm. AEs that occurred in greater than 5% of patients in the fruquintinib arm vs the placebo arm were hypertension (13.6% vs 0.9%), asthenia (7.7% vs 3.9%), and hand-foot syndrome (6.4% vs 0%).


1. HUTCHMED completes rolling submission of NDA to U.S. FDA for fruquintinib for the treatment of refractory metastatic colorectal cancer. News release. HUTCHMED. March 31, 2023. Accessed April 3, 2023. https://bit.ly/3lWX2R3

2. National center for biotechnology information. PubChem compound summary for CID 44480399, fruquintinib. Accessed April 3, 2023. https://pubchem.ncbi.nlm.nih.gov/compound/Fruquintinib.

3. Dasati NA, Lonardi S, Garcia-Carbonero R, et al. LBA25 - FRESCO-2: A global phase III multiregional clinical trial (MRCT) evaluating the efficacy and safety of fruquintinib in patients with refractory metastatic colorectal cancer. Ann oncol. 2022;33 (suppl_7): S808-S869. doi:10.1016/annonc/annonc1089

Related Videos
Rohit Gosain, MD; Rahul Gosain, MD; and Pamela L. Kunz, MD, presenting slides
Rohit Gosain, MD; Rahul Gosain, MD; and Pamela L. Kunz, MD, presenting slides
Related Content