A New Treatment Option for Metastatic Colorectal Cancer – Fruquintinib Receives FDA Approval

For adult patients with metastatic colorectal cancer (mCRC) previously treated with fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy, an anti-VEGF treatment and, if RAS wild-type and medically appropriate, an anti-EGFR treatment, fruquintinib (Fruzaqla, Takeda Pharma.) received FDA (US Food and Drug Administration) approval on 8 November 2023.

How Does Fruquintinib Work?

Fruquintinib is an oral tyrosine kinase inhibitor used to treat metastatic colorectal cancer. Its mechanism of action targets vascular endothelial growth factor (VEGF) pathways, which play a critical role in the growth and spread of cancer cells. VEGF enables tumours to form new blood vessels (angiogenesis), supporting their nourishment and growth. By blocking VEGF receptors, fruquintinib suppresses this process, restricting tumour growth and reducing the ability of cancer cells to metastasise. Through this mechanism, it is used especially to control metastatic colorectal cancer cells resistant to other treatments.

FDA Approval Through the FRESCO-2 Study

Efficacy was evaluated in the FRESCO-2 and FRESCO studies.

FRESCO-2, an international, multicentre, randomised, double-blind, placebo-controlled study, evaluated 691 patients with mCRC whose disease had progressed after fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy, an anti-VEGF biological treatment and, if RAS wild-type, an anti-EGFR biological treatment, and at least one of trifluridine/tipiracil or regorafenib.

The multicentre, placebo-controlled FRESCO study, conducted in China, evaluated 416 patients with metastatic colorectal cancer whose disease had progressed after fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy.

In both studies, patients were randomly assigned to receive either oral fruquintinib 5 mg once daily or placebo plus best supportive care (2:1) for the first 21 days of each 28-day cycle.

Patients received treatment until disease progression or unacceptable toxicity.

The main efficacy outcome in both studies was overall survival.

Results

• In FRESCO-2, median overall survival in patients treated with fruquintinib was 7.4 months (95% CI: 6.7, 8.2), compared with 4.8 months in the placebo group (95% CI: 4.0, 5.8) (HR 0.66 [95% CI: 0.55, 0.80], p-value < 0.001).
• In FRESCO, median overall survival in the respective treatment arms was 9.3 months (95% CI: 8.2, 10.5) and 6.6 months (95% CI: 5.9, 8.1) (HR 0.65 [95% CI: 0.51, 0.83], p-value < 0.001).

The most common adverse reactions (reported in more than 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.