FDA Approves Fruquintinib for Previously Treated Metastatic Colorectal Cancer


Fruquintinib is a new, well-tolerated option for the treatment of patients with refractory metastatic colorectal cancer.

  • Fruquintinib is a highly selective and potent oral tyrosine kinase inhibitor of VEGFR-1, -2, and -3.
  • Findings from the phase 3 FRESCO-2 study (NCT04322539) support this regulatory decision.
  • FRESCO-2 is the first study to show efficacy of an oral VEGFR inhibitor in patients who have previously been treated with trifluridine-tipiracil, regorafenib, or both.

The FDA has approved fruquintinib (HMPL-013) for the treatment of patients with metastatic colorectal cancer (mCRC) who have been previously treated with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, an anti-VEGF therapy, and, if RAS wild-type and medically appropriate, an anti-EGFR therapy.1

Data from the FRESCO-2 study showed that treatment with fruquintinib reduced the risk of death by 34% in patients with refractory mCRC and the median overall survival with fruquintinib observed in the study was 7.4 months vs 4.8 months with best supportive care (BSC), representing a significant improvement (HR, 0.66; 95% CI, 0.55-0.80; P < .0001).

These results from FRESCO-2 serve as the basis for the regulatory decision.

"This is a drug that's proven to be effective, both in the third-line setting as well as the refractory setting after patients progressed on everything else that's available. That's putting data together from the original FRESCO trial done in China, as well as the FRESCO-2 trial," Arvind Dasari, MD, MS, associate professor in the Department of Gastrointestinal Medical Oncology in the Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center in Houston, Texas, told Targeted OncologyTM.

Colorectal cancer image: © mi_viri - stock.adobe.comNormal

Colorectal cancer image: © mi_viri - stock.adobe.comNormal

Fruquintinib is a selective inhibitor of VEGFR-1, -2, and -3 that previously has shown to inhibit the migration, proliferation, and survival of endothelial cells as well as inhibit microvessel formation, tumor cell proliferation, and tumor cell death.

The randomized, double-blind, placebo-controlled, phase 3 study enrolled 691 patients with refractory mCRC in the United States, Europe, Japan, and Australia. Patients were given fruquintinib in combination with BSC or placebo and BSC with oral fruquintinib or placebo dosed at 5 mg once daily for 3 weeks in 28-day cycles. The median duration of treatment in the study was 11.3 months in the fruquintinib arm and 11.2 months in the placebo arm.

Additional findings from the study showed that the median progression-free survival (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). At 6 months, the PFS rate was 24% for patients in the fruquintinib group vs 1% in the placebo group.

For the other efficacy end points, fruquintinib showed an overall response rate of 1.5% vs 0% with placebo. Notably, the disease control rate (DCR) with fruquintinib was 56%.

Among patients treated with fruquintinib, 62.7% of patients had a grade 3 or higher adverse event (AE) 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%).

Overall, fruquintinib was well-tolerated in this heavily pretreated patient population.

“Patients with metastatic disease are often fragile and fatigued – due to both their condition as well as the therapies they have been exposed to. An oral, chemotherapy-free option that offers a survival benefit despite treatment with prior therapies is a critical need for treating metastatic colorectal cancer,” said Cathy Eng, MD, FACP, at Vanderbilt University Medical Center, said in a press release.1 “Colorectal cancer is a highly heterogeneous disease, making it difficult to bring advancements to patients whose cancer has metastasized. I look forward to being able to offer a new solution to appropriate patients.”

  1. Takeda Receives U.S. FDA Approval of FRUZAQLA™ (fruquintinib) for Previously Treated Metastatic Colorectal Cancer. Takeda. News release. November 8, 2023. Accessed November 8, 2023. https://tinyurl.com/2rkwetvu
  2. 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
  3. Dasari A, Lonardi S, Garcia-Carbonero R, et al. Fruquintinib versus placebo in patients with refractory metastatic colorectal cancer (FRESCO-2): an international, multicentre, randomised, double-blind, phase 3 study. Lancet. 2023;402(10395):41-53. doi:10.1016/S0140-6736(23)00772-9
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