Fruquintinib Wins European Approval for Pretreated mCRC


Key Takeaways

  • Fruquintinib is approved for mCRC patients previously treated with standard therapies, including TAS-102 or regorafenib.
  • The FRESCO-2 trial showed fruquintinib significantly improved OS (7.4 months vs 4.8 months) and PFS (3.7 months vs 1.8 months) compared to placebo.
Josep Tabernero, MD, PhD

Josep Tabernero, MD, PhD

The European Commission (EC) has approved fruquintinib (Fruzaqla) monotherapy for the treatment of adult patients with metastatic colorectal cancer (mCRC) who have been previously treated with available standard therapies, including fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, anti-VEGF agents, and anti-EGFR agents, and who have progressed on or are intolerant to treatment with either trifluridine plus tipiracil (TAS-102; Lonsurf) or regorafenib (Stivarga).1

The regulatory decision was supported by data from the phase 3 FRESCO-2 trial (NCT04322539), which showed that treatment with fruquintinib led to a statistically significant and clinically meaningful improvement in overall survival (OS) compared with placebo in patients with refractory mCRC (HR, 0.66; 95% CI, 0.55-0.80; P < .0001).2 At a median follow-up of 11.3 months (interquartile range [IQR], 9.0-14.2) in the fruquintinib group and 11.2 months (IQR, 8.7-15.5) in the placebo group, fruquintinib (n = 461) elicited a median OS of 7.4 months (95% CI, 6.7-8.2) vs 4.8 months (95% CI, 4.0-5.8) for placebo (n = 230).

“With fruquintinib being the first and only selective inhibitor of all three VEGFRs to be approved in the European Union for CRC, this decision represents a significant milestone in European oncology,” Josep Tabernero, MD, PhD, director of Vall d´Hebron Institute of Oncology, stated in a news release.1 “There is a clear need in Europe for patients and their clinicians to be able to access a new treatment option for previously treated metastatic colorectal cancer, and we are excited that this important step has been taken so that we can begin prescribing this new and differentiated medicine.”

In April 2024, the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) recommended the approval of fruquintinib for the treatment of adult patients with previously treated mCRC.3 In November 2023, the FDA approved fruquintinib for the treatment of adult patients with 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.4

The FDA approval was also supported in part by data from FRESCO-2, which was an international, randomized, double-blind, placebo-controlled study that enrolled patients at least 18 years of age (or at least 20 years of age in Japan) who had histologically or cytologically documented metastatic colorectal adenocarcinoma and previously received all standard, approved cytotoxic and targeted therapies and progressed on or were intolerant to TAS-102 and/or regorafenib.2

Patients were randomly assigned in a 2:1 fashion to receive 5 mg of oral fruquintinib or placebo once per day on days 1 to 21 of each 28-day cycle, in combination with best supportive care. Treatment was given until disease progression, death, unacceptable toxicity, patient withdrawal, discontinuation by the physician, or study completion or termination.

Stratification factors included previous therapy (TAS-102 vs regorafenib vs both), RAS status (mutated vs wild-type), and duration of metastatic disease (≤18 months vs >18 months).

OS served as the trial’s primary end point. Secondary end points included investigator-assessed progression-free survival (PFS) per RECIST 1.1 criteria, objective response rate, disease control rate, duration of response, and safety.

Additional data showed the patients treated with fruquintinib achieved a median PFS of 3.7 months (95% CI, 3.5-3.8) vs 1,8 months (95% CI, 1.8-1.9) for those given placebo (HR, 0.32; 95% CI, 0.27-0.39; P < .0001).

The ORR was 2% (95% CI, 0.6%-3.1%) in the fruquintinib group vs 0% (95% CI, 0.0%-1.6%) in the placebo group. The respective DCRs were 56% (95% CI, 50.9%-60.1%) and 16% (95% CI, 11.6-21.5%). The median DOR was 10.7 months (95% CI, 3.9–not evaluable; range, 2.1-16.9) in the experimental arm.

Regarding safety, any-grade adverse effects (AEs) occurred in 99% of evaluable patients in the fruquintinib group (n = 456) vs 93% of patients in the placebo group (n = 230). The rates of grade 3 or higher AEs were 63% and 50%, respectively. AEs led to death in 11% of patients in the fruquintinib arm vs 20% of patients in the placebo arm; notably, disease progression was the most frequently reported AE leading to death in each arm (7% vs 13%).

In the fruquintinib arm, the rates of AEs that led to dose interruptions, dose reductions, and treatment discontinuation were 47%, 24%, and 20%, respectively. These respective rates were 27%, 4%, and 21% in the placebo arm.

“We are delighted to have achieved EC approval for [fruquintinib] and that we can now offer a new therapeutic option for patients with previously treated mCRC, regardless of their biomarker status,” Teresa Bitetti, president of the Global Oncology Business Unit at Takeda, added in a news release.1 “Patients in Europe with mCRC have long needed additional treatment options, and we are grateful to be able to meet that need thanks to our partnership with HUTCHMED.”


  1. HUTCHMED announces European Commission approval for Fruzaqla (fruquintinib) received by Takeda. News release. HUTCHMED. June 21, 2024. Accesed June 24, 2024.
  2. 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
  3. Takeda receives positive CHMP opinion for fruquintinib in previously treated metastatic colorectal cancer. News release. Takeda. April 26, 2024. Accessed June 24, 2024.
  4. FDA approves fruquintinib in refractory metastatic colorectal cancer. FDA. November 8, 2023. Accessed June 24, 2024.
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