Fruquintinib in Practice: Nuances of Treatment Management and Future Combination Approaches

Fruquintinib, a newer VEGFR inhibitor for metastatic colorectal cancer, requires careful dose management and patient monitoring due to its toxicity profile, particularly hypertension and fatigue. The standard 5 mg daily dose may not be appropriate for all patients, especially those with ECOG performance status of 2, who often experience significant asthenia and fatigue requiring dose modifications. Early intervention strategies include home blood pressure monitoring and readily available antihypertensive medications to manage grade 3 hypertension.

Clinical experience suggests starting with lower doses (3-4 mg) in frail or elderly patients, followed by intrapatient dose escalation similar to other tyrosine kinase inhibitors. This approach is challenging due to the available pill sizes (1 mg and 5 mg), leading some practitioners to request more flexible dosing options from manufacturers. The strategy of starting low and titrating up appears to improve tolerability while potentially maintaining efficacy, though this approach is based on limited data from small studies in elderly populations.

Future research directions include investigating optimal dosing in randomized trials, particularly for elderly patients or those with poor performance status. The panel emphasizes the need for postmarketing studies to determine whether lower maintenance doses (3-4 mg) might provide adequate disease control with better quality of life. Combination studies with TAS-102 are showing promising early results with response rates of 10% to 18% in refractory settings, potentially offering new treatment paradigms for patients with advanced colorectal cancer.