The European Commission has approved Fruzaqla (fruquintinib; Takeda) as a monotherapy for the treatment of adult patients with metastatic colorectal cancer (mCRC). The approval is for those who have been previously treated with available standard therapies — including fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapies, anti–vascular endothelial growth factor (VEGF) agents, and anti–epidermal growth factor receptor agents — and who have progressed on or are intolerant to treatment with either trifluridine-tipiracil or regorafenib.
The decision follows a positive opinion for the drug from the European Medicines Agency Committee for Medicinal Products for Human Use in April this year.
Fruquintinib is a kinase inhibitor that works by inhibiting tumor angiogenesis. As a selective oral inhibitor of VEGFR-1, -2, and -3, it effectively blocks the pathways that facilitate blood vessel formation in tumors. It is the first novel targeted therapy in the European Union for mCRC regardless of biomarker status in more than a decade.
Among patients with new colorectal cancer diagnoses, 20% have metastatic disease at presentation. Another 25% who present with localized disease will later develop metastases. Whereas early-stage CRC can be surgically resected, mCRC remains an area of high unmet need, with poor outcomes and limited treatment options.
A New Treatment Choice
The approval is based on results from the phase 3 multiregional FRESCO-2 trial. This trial investigated fruquintinib vs placebo, plus best supportive care in both groups, in patients with previously treated mCRC.
Treatment with fruquintinib resulted in a significant and clinically meaningful benefit in overall survival compared with placebo in patients with refractory mCRC, regardless of the prior types of therapies they received.
Median overall survival was 7.4 months in the treatment group compared with 4.8 months in the placebo group.
The study's authors wrote that the data supported the use of fruquintinib as a global treatment option for patients with refractory mCRC.
Adverse reactions leading to treatment discontinuation occurred in 20% of patients treated with fruquintinib vs 21% of those treated with placebo.
The most commonly reported adverse reactions from fruquintinib — with a frequency of at least 1 in 10 patients — are thrombocytopenia; hypothyroidism; anorexia; hypertension; dysphonia; diarrhea; stomatitis; palmar-plantar erythrodysesthesia syndrome; musculoskeletal discomfort; arthralgia; proteinuria; asthenia; fatigue; and increased levels of aspartate aminotransferase, total bilirubin, and alanine aminotransferase.
"People living with metastatic colorectal cancer face numerous difficulties, stemming both from their illness and the adverse effects of therapies," said Josep Tabernero, MD, PhD, director of Vall d'Hebron Institute of Oncology, Barcelona, Spain, in a press release. "Given the complex nature of the disease, introducing innovative treatments such as fruquintinib — an oral, chemotherapy-free targeted agent — is essential."