General Information

Fruzaqla (fruquintinib) is a kinase inhibitor.

 Fruzaqla is specifically indicated for the treatment of adult 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.

Fruzaqla is supplied as capsules for oral administration. The recommended dose is 5 mg orally once daily, with or without food for the first 21 days of each 28-day cycle.

Mechanism of Action

Fruzaqla (fruquintinib) is a small molecule kinase inhibitor of vascular endothelial growth factor receptors (VEGFR)-1, -2, and -3 with IC50 values of 33, 35, and 0.5 nM, respectively. In vitro studies showed fruquintinib inhibited VEGF-mediated endothelial cell proliferation and tubular formation. In vitro and in vivo studies showed fruquintinib inhibited VEGF-induced VEGFR-2 phosphorylation. In vivo studies showed fruquintinib inhibited tumor growth in a tumor xenograft mouse model of colon cancer.

Side Effects

Adverse effects associated with the use of Fruzaqla may include, but are not limited to, the following:

• hypertension
• palmar-plantar erythrodysesthesia
• proteinuria
• dysphonia
• abdominal pain
• diarrhea
• asthenia

Clinical Trial Results

FDA approval of Fruzaqla was based on FRESCO-2 and FRESCO.  FRESCO-2, an international, multicenter randomized, double-blind, placebo-controlled trial, 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 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 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 therapy until disease progression or toxicity. 

Overall survival (OS) was the major efficacy outcome in both trials. In FRESCO-2, median OS was 7.4 months for those treated with fruquintinib and 4.8 months in the placebo group. In FRESCO, median OS was 9.3 months and 6.6 months in the respective treatment arms.