Presented by Prof Eric Van Cutsem (University Hospitals Leuven) and Prof Marc Van den Eynde (Cliniques Universitaires Saint-Luc)
The SUNLIGHT trial undertook a comparative investigation of metastatic colorectal cancer treatment, evaluating the classical trifluridine–tipiracil (FTD–TPI) regimen with or without the addition of bevacizumab, a VEGF-inhibitor. Enrolled patients had previously undergone one or two discontinued chemotherapy regimens due to disease progression or intolerable side effects, placing them within a classic third-line patient cohort. The primary endpoint was overall survival (OS), with secondary endpoints encompassing progression-free survival (PFS) and safety.
The trial unequivocally revealed a median OS benefit exceeding 3 months, coupled with enhanced PFS and an extended time to deterioration in the combination group. This positive outcome was consistently observed across all patient populations, irrespective of subgroups: the findings remained independent of RAS status, prior bevacizumab treatment, and other factors. As expected, the combination of FTD-TPI and bevacizumab exhibited no additional toxicity.
Consequently, this study establishes a new standard in the third-line treatment landscape for metastatic colorectal cancer patients. The New England Journal of Medicine published the results, leading to approval by the European Medicines Agency (EMA) and subsequent integration into updated guidelines. Molecular characterization is deemed crucial in third-line scenarios, particularly for assessing BRAF mutation status or HER2 amplified tumours, where targeted therapy is warranted. However, in the absence of specific molecular alterations, this FTD-TPI and bevacizumab combination emerges as the optimal choice in clinical practice.
Experts concur on the remarkable magnitude of benefit observed in this study, with a 3-month increase in OS unprecedented even in earlier treatment protocols. Insights from these data suggest that, in patients lacking specific molecular alterations, the addition of angiogenesis inhibitors to cytotoxic agents yields an augmentative effect. This effect persists irrespective of prior bevacizumab use, indicating that angiogenesis inhibition contributes significantly to cytotoxic treatment efficacy across various treatment lines. While acknowledging that this conclusion is drawn from a single study, the discernible effect in a sizable patient cohort is evident.
The consensus among experts is that the FTD-TPI and bevacizumab regimen stands as the new standard of care, particularly in later lines and for patients lacking specific molecular alterations. Given the consistent and substantial benefits across various endpoints, any novel treatment options necessitate direct comparison with this combination.
References:
Prager GW. et al. (2023) Trifluridine–Tipiracil and Bevacizumab in Refractory Metastatic Colorectal Cancer. N Engl J Med 388:1657-1667