On November 8, 2023, fruquintinib (Fruzaqla) was approved for adults with metastatic colorectal cancer 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.1
Supporting Efficacy Data
Approval was supported by the international FRESCO-2 trial (ClinicalTrials.gov identifier NCT04322539) and the Chinese FRESCO trial (NCT02314819). FRESCO-2 included 691 patients with disease progression during or after prior fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy; an anti-VEGF biological therapy; an anti-EGFR biological therapy if RAS wild-type; and at least one course of trifluridine/tipiracil or regorafenib. FRESCO included 416 patients with disease progression during or after prior fluoropyrimidine-, oxaliplatin, and irinotecan-based chemotherapy. In both trials, patients were randomly assigned 2:1 to receive oral fruquintinib at 5 mg once daily or placebo for the first 21 days of each 28-day cycle plus best supportive care, with treatment continuing until disease progression or unacceptable toxicity.
In FRESCO-2, the median overall survival was 7.4 months (95% confidence interval [CI] = 6.7–8.2 months) in the fruquintinib group vs 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, the median overall survival was 9.3 months (95% CI = 8.2–10.5 months) in the fruquintinib group vs 6.6 months (95% CI = 5.9–8.1 months) in the placebo group (HR = 0.65, 95% CI = 0.51–0.83, P < .001).
How It Is Used
The recommended fruquintinib dose is 5 mg once daily for the first 21 days of each 28-day cycle until disease progression or unacceptable toxicity.
Safety Profile
Product labeling provides safety data for both FRESCO-2 and FRESCO. Among the FRESCO-2 safety population of 456 patients in the fruquintinib group and 230 patients in the placebo group, the most common adverse events of any grade occurring at a 5% or higher incidence in the fruquintinib group were fatigue (53% vs 29%), hypertension (38% vs 9%), stomatitis (31% vs 7.8%), abdominal pain (25% vs 20%), and hypothyroidism (21% vs 0.4%). Serious adverse events occurred in 38% of the fruquintinib group, most commonly hemorrhage (2.2%) and gastrointestinal perforation (2.0%).
OF NOTE
Fruquintinib has warnings/precautions for hypertension, hemorrhagic events, infections, gastrointestinal perforation, hepatotoxicity, proteinuria, palmar-plantar erythrodysesthesia, posterior reversible encephalopathy syndrome, impaired wound healing, arterial thromboembolic events, allergic reactions to FD&C Yellow No. 5 and No. 6, and embryofetal toxicity.
Fruquintinib has warnings/precautions for hypertension, hemorrhagic events, infections, gastrointestinal perforation, hepatotoxicity, proteinuria, palmar-plantar erythrodysesthesia, posterior reversible encephalopathy syndrome, impaired wound healing, arterial thromboembolic events, allergic reactions to FD&C Yellow No. 5 (tartrazine) and No. 6 (sunset yellow FCF), and embryofetal toxicity. Concomitant use with strong or moderate CYP3A inducers (phenobarbital, phenytoin, rifampicin) should be avoided. Patients should be advised not to breastfeed while receiving fruquintinib.
REFERENCE
1. Fruzaqla (fruquintinib) capsules, for oral use, prescribing information, Takeda Pharmaceuticals USA, November 2023. Available at http://www.accessdata.fda.gov/drugsatfda_docs/label/2023/217564s000lbl.pdf. Accessed January 4, 2023.
