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FDA Approval Summary: Fruquintinib for the Treatment of Refractory Metastatic Colorectal Cancer
Michael J Fusco1, Sandra J Casak1, Sirisha L Mushti1
1Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland.
Abstract:
On November 8, 2023, the FDA approved fruquintinib, an inhibitor of vascular endothelial growth factor receptor (VEGFR)-1, -2, and -3, 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. Approval was based on Study FRESCO-2, a globally conducted, double-blind, placebo-controlled randomized trial. The primary endpoint was overall survival (OS). The key secondary endpoint was progression-free survival. A total of 691 patients were randomly assigned (461 and 230 into the fruquintinib and placebo arms, respectively). Fruquintinib provided a statistically significant improvement in OS with a hazard ratio (HR) of 0.66 [95% confidence interval (CI), 0.55, 0.80; P < 0.001]. The median OS was 7.4 months (95% CI, 6.7, 8.2) in the fruquintinib arm and 4.8 months (95% CI, 4.0, 5.8) for the placebo arm. Adverse events observed were generally consistent with the known safety profile associated with the inhibition of VEGFR. The results of FRESCO-2 were supported by the FRESCO study, a double-blind, single-country, placebo-controlled, randomized trial in patients with refractory mCRC who have been previously treated with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy. In FRESCO, the OS HR was 0.65 (95% CI, 0.51, 0.83; P < 0.001). FDA concluded that the totality of the evidence from FRESCO-2 and FRESCO supported an indication for patients with mCRC with prior treatment with fluoropyrimidine, oxaliplatin-, and irinotecan-based chemotherapy, an anti-VEGF biological therapy, and if RAS wild-type and medically appropriate, an anti-EGFR therapy.
Insights
The FDA approved fruquintinib for metastatic colorectal cancer (mCRC) after prior treatments. This vascular endothelial growth factor receptor (VEGFR) inhibitor significantly improved overall survival in patients with refractory mCRC.
Area of Science:
- Oncology
- Pharmacology
- Clinical Trials
Background:
- Metastatic colorectal cancer (mCRC) presents a significant therapeutic challenge, particularly in patients refractory to standard chemotherapy and targeted therapies.
- Vascular Endothelial Growth Factor Receptor (VEGFR) signaling is crucial for tumor angiogenesis and progression in mCRC.
- Previous treatment regimens for mCRC often include fluoropyrimidine, oxaliplatin, irinotecan, anti-VEGF, and anti-EGFR therapies.
Purpose of the Study:
- To evaluate the efficacy and safety of fruquintinib in patients with previously treated metastatic colorectal cancer (mCRC).
- To determine if fruquintinib improves overall survival (OS) and progression-free survival (PFS) compared to placebo in refractory mCRC.
- To support the FDA approval of fruquintinib for a specific patient population with advanced mCRC.
Main Methods:
- Study FRESCO-2 was a global, double-blind, placebo-controlled, randomized trial involving 691 patients with refractory mCRC.
- Patients received either fruquintinib or a placebo, in addition to best supportive care.
- The primary endpoint was overall survival (OS), with progression-free survival (PFS) as a key secondary endpoint.
Main Results:
- Fruquintinib demonstrated a statistically significant improvement in OS, with a hazard ratio (HR) of 0.66 (95% CI, 0.55-0.80; P < 0.001).
- Median OS was 7.4 months for fruquintinib versus 4.8 months for placebo.
- The FRESCO study results corroborated these findings, showing an OS HR of 0.65 (95% CI, 0.51-0.83; P < 0.001) in a similar patient population.
Conclusions:
- Fruquintinib significantly enhances overall survival in patients with metastatic colorectal cancer (mCRC) who have undergone prior treatments.
- The safety profile of fruquintinib is consistent with its mechanism of action as a VEGFR inhibitor.
- The combined evidence from FRESCO-2 and FRESCO supports fruquintinib's indication for refractory mCRC patients meeting specific treatment history criteria.
