Episode 6: Fruquintinib, a new drug in refractory, metastatic colorectal cancer: results from the FRESCO-2 trial
Presented by Prof Eric Van Cutsem (University Hospitals Leuven) and Prof Marc Van den Eynde (Cliniques Universitaires Saint-Luc)
The absence of efficacious interventions for advanced, chemotherapy-refractory colorectal cancer necessitates the exploration of novel therapeutic agents. In this context, fruquintinib was investigated in a phase 3 study involving heavily pretreated patients who had experienced progression on or intolerance to trifluridine-tipiracil or regorafenib. Fruquintinib, functioning as a tyrosine kinase inhibitor targeting VEGFR 1, 2, and 3, was administered orally at a dosage of 5 mg over 21 days within a 28-day regimen.
A total of over 690 patients were randomized in a 2:1 ratio to receive either fruquintinib or placebo. The primary endpoint of the study was OS. The results unequivocally demonstrated an OS advantage with fruquintinib over placebo, manifesting as a noteworthy increase in median survival from 4.8 to 7.4 months within this patient cohort. Additional pertinent efficacy parameters, encompassing disease control, PFS and safety were systematically assessed. Notably, safety profiles were favourable, with a relatively low incidence of dose reduction or treatment discontinuation. While fruquintinib did not induce objective tumour regression responses, it exhibited superior disease control compared to the placebo. These significant findings have recently been published in The Lancet.
Experts are deliberating on the prospective role of fruquintinib in the metastatic colorectal cancer treatment landscape. A new standard third-line treatment was presented in the SUNLIGHT trial, using trifluridine-tipiracil and bevacizumab. Fruquintinib appears to find its place in the treatment continuum, given that patients in the FRESCO-2 study, where fruquintinib was employed, had undergone a median of three prior treatments, situating this drug in the fourth-line setting. The evolving standard in the third line, involving trifluridine-tipiracil and bevacizumab, further underscores the potential positioning of fruquintinib in the fourth-line context.
Comparative analyses with regorafenib have not been performed, preventing conclusive determinations regarding superiority or inferiority. The sequencing of regorafenib followed by fruquintinib, or vice versa, remains an open question due to the limited experience with fruquintinib and will be the physician’s choice. Nonetheless, insights from the current trial and a preceding Chinese randomized phase 2 study (FRESCO) affirm the acceptable toxicity profile and safety of fruquintinib. While awaiting regulatory approval, it is anticipated that fruquintinib will likely assume a sequential role following trifluridine-tipiracil and bevacizumab in clinical practice.
References:
Dasari A. et al. (2023) Fruquintinib versus placebo in patients with refractory metastatic colorectal cancer (FRESCO-2): an international, multicentre, randomised, double-blind, phase 3 study. The Lancet 402 (10395): 41-537