FDA Approval Summary: Fruquintinib for the Treatment of Refractory Metastatic Colorectal Cancer.

On November 8, 2023, the FDA approved fruquintinib, an inhibitor of vascular endothelial growth factor receptors (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 (PFS). A total of 691 patients were randomized (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% 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 inhibition of the 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.