A phase 3 clinical trial confirms that combination therapy with trifluridine–tipiracil plus bevacizumab is associated with better clinical outcomes in refractory colorectal cancer cases than trifluridine–tipiracil monotherapy.
First-line and second-line treatment of colorectal cancer includes chemotherapy with fluorouracil-based agents (oxaliplatin and irinotecan) along with newer vascular endothelial growth factor (VEGF)-based therapy (mainly bevacizumab) and epidermal growth factor receptor (EGFR) therapies. Nonetheless, some patients continue to progress after receiving these therapies. Many of these patients have good performance status and might be considered for reintroduction of chemotherapeutic agents.
This phase 3 study, known as the SUNLIGHT trial, aimed to assess the efficacy and safety of combining trifluridine–tipiracil (FTD–TPI) with bevacizumab compared to FTD–TPI alone in patients with refractory metastatic colorectal cancer. The study’s findings are published in the New England Journal of Medicine.
FTD–TPI Plus Bevacizumab Therapy Offers Hope
The study included refractory colorectal cancer patients. These were patients who had previously received no more than two chemotherapy regimens and had experienced either progressive disease or unacceptable adverse effects. Previous treatments included fluoropyrimidine, irinotecan, oxaliplatin, anti-VEGF monoclonal antibody, or anti-EGFR monoclonal antibody (for patients with RAS wild-type disease), and participants had an Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1.
Since the primary aim of the study was to compare the outcomes of monotherapy with FTD–TPI to FTD–TPI plus bevacizumab, patients were randomly divided into two groups. The primary endpoint was overall survival, and secondary endpoints included progression-free survival, objective response, disease control, quality of life, and safety.
Overall, 492 patients were enrolled in the study. The combination of FTD–TPI and bevacizumab significantly improved overall survival compared to FTD–TPI alone (median overall survival: 10.8 months in the combination group vs. 7.5 months in the FTD–TPI group (hazard ratio for death: 0.61; p < 0.001). Similarly, progression-free survival was significantly longer in the combination group than in the FTD–TPI group, at 5.6 months vs. 2.4 months, respectively (hazard ratio for disease progression or death: 0.44; p < 0.001).
Adverse effects, including neutropenia, nausea, and anemia, were common in both groups. Severe adverse effects resulted in therapy discontinuation in 12.6% of the participants in both the combination and FTD–TPI groups.
The Bottom Line
The SUNLIGHT trial demonstrated the superiority of FTD–TPI plus bevacizumab over monotherapy with FTD–TPI in colorectal cancer refractory cases. One of the stated limitations of the study was the underrepresentation of Black patients. The combination therapy helped significantly increase overall survival and progression-free survival and showed a manageable safety profile, with adverse events primarily related to myelosuppression. Hence, this combination therapy can be considered in refractory cases.
Source:
Prager, G. W., Taı̈Eb, J., Fakih, M., Ciardiello, F., Van Cutsem, É., Élez, E., Cruz, F. M., Wyrwicz, L., Stroyakovskiy, D., Pápai, Z., Poureau, P., Liposits, G., Cremolini, C., Bondarenko, I., Modest, D. P., Benhadji, K. A., Amellal, N., Leger, C., Vidot, L., & Tabernero, J. (2023). Trifluridine–Tipiracil and bevacizumab in refractory metastatic colorectal cancer. The New England Journal of Medicine, 388(18), 1657–1667. https://doi.org/10.1056/nejmoa2214963
