On 8 November 2023, the US Food and Drug Administration (FDA) approved fruquintinib (Fruzaqla, Takeda Pharmaceuticals, Inc.) for adult patients with metastatic colorectal cancer (mCRC) who received prior fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, an anti-VEGF therapy, and, if RAS wild-type and medically appropriate, an anti-EGFR therapy.

Full prescribing information for fruquintinib is available here.

Efficacy was evaluated in FRESCO-2 (NCT04322539) and FRESCO (NCT02314819). FRESCO-2 (NCT04322539), an international, multicentre, randomised, double-blind, placebo-controlled study, evaluated 691 patients with mCRC who had disease progression during or after prior fluoropyrimidine-, oxaliplatin-, irinotecan-based chemotherapy, an anti-VEGF biological therapy an anti-EGFR biological therapy if RAS wild-type, and at least one of trifluridine/tipiracil or regorafenib. FRESCO, a multicentre, placebo-controlled study conducted in China, evaluated 416 patients with mCRC who had disease progression during or after prior fluoropyrimidine-, oxaliplatin, and irinotecan-based chemotherapy.

In both studies patients were randomly allocated (2:1) to either fruquintinib 5 mg orally once daily or placebo for the first 21 days of each 28-day cycle plus best supportive care. Patients received treatment until disease progression or unacceptable toxicity.

Overall survival (OS) was the major efficacy outcome in both studies. In FRESCO-2, median OS was 7.4 months (95% confidence interval [CI] 6.7, 8.2) for those treated with fruquintinib and 4.8 months (95% CI 4.0, 5.8) in the placebo group (hazard ratio [HR] 0.66, 95% CI 0.55, 0.80; p-value < 0.001). In FRESCO, median OS was 9.3 months (95% CI 8.2, 10.5) and 6.6 months (95% CI 5.9, 8.1) in the respective treatment arms (HR 0.65, 95% CI 0.51, 0.83; p-value < 0.001).

The most common adverse reactions (reported in ≥20% of patients) were hypertension, palmar-plantar erythrodysesthesia, proteinuria, dysphonia, abdominal pain, diarrhoea, 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 (OCE). Project Orbis provides a framework for concurrent submission and review of oncology drugs among international partners. For this review, 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 granted priority review.

Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System.

For assistance with single-patient INDs for investigational oncology products, healthcare professionals may contact OCE’s Project Facilitate.