On November 8, the U.S. Food and Drug Administration (FDA) approved fruquintinib (Fruzaqla) for adult patients with metastatic colorectal cancer who received prior fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy; an anti-VEGF therapy; and—if their disease is RAS wild-type and it was deemed medically appropriate—an anti-EGFR therapy.
FRESCO-2 and FRESCO Trials
Efficacy was evaluated in the FRESCO-2 (ClinicalTrials.gov identifier NCT04322539) and FRESCO (NCT02314819) trials.
FRESCO-2—an international, multicenter, randomized, double-blind, placebo-controlled trial—evaluated 691 patients with metastatic colorectal cancer who had disease progression during or after prior fluoropyrimidine-, oxaliplatin-, irinotecan-based chemotherapy; an anti-VEGF biological therapy; an anti-EGFR biological therapy if they were RAS wild-type; and at least one course of trifluridine/tipiracil or regorafenib.
FRESCO, a multicenter, placebo-controlled trial conducted in China, evaluated 416 patients with metastatic colorectal cancer who had disease progression during or after prior fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy.
In both trials, patients were randomly allocated 2:1 to receive either fruquintinib at 5 mg orally once daily or placebo for the first 21 days of each 28-day cycle plus best supportive care. Patients received therapy until disease progression or unacceptable toxicity.
Overall survival was the major efficacy outcome in both trials. In FRESCO-2, median overall survival was 7.4 months (95% confidence interval [CI] = 6.7–8.2 months) for those treated with fruquintinib and 4.8 months (95% CI = 4.0–5.8 months) in the placebo group (hazard ratio [HR] = 0.66, 95% CI = 0.55–0.80, P < .001). In FRESCO, median overall survival was 9.3 months (95% CI = 8.2–10.5 months) and 6.6 months (95% CI = 5.9–8.1 months) in the respective treatment arms (HR = 0.65, 95% CI = 0.51–0.83, P < .001).
The most common adverse reactions (reported in ≥ 20% of patients) were hypertension, palmar-plantar erythrodysesthesia, proteinuria, dysphonia, abdominal pain, diarrhea, and asthenia.
The recommended fruquintinib dose is 5 mg orally once daily, with or without food, for the first 21 days of each 28-day cycle until disease progression or unacceptable toxicity.
This review was conducted under Project Orbis, an initiative of the FDA Oncology Center of Excellence. Project Orbis provides a framework for concurrent submission and review of oncology drugs among international partners. For this review, the FDA collaborated with the Australian Therapeutic Goods Administration, Health Canada, Singapore’s Health Sciences Authority, Switzerland’s Swissmedic, and United Kingdom’s Medicines and Healthcare products Regulatory Agency. The application reviews are ongoing at the other regulatory agencies.
This application was also granted Priority Review.
