As reported in The New England Journal of Medicine by Prager et al, the phase III SUNLIGHT trial has shown prolonged overall survival with the addition of bevacizumab to trifluridine/tipiracil (FTD-TPI) in previously treated patients with metastatic colorectal cancer.
As stated by the investigators, “In a previous phase III trial, treatment with FTD-TPI prolonged overall survival among patients with metastatic colorectal cancer. Preliminary data from single-group and randomized phase II trials suggest that treatment with FTD-TPI in addition to bevacizumab has the potential to extend survival.”
Study Details
In the trial, 492 patients from sites in 13 countries were randomly assigned between November 2020 and February 2022 to receive FTD-TPI twice daily at a starting dose of 35 mg/m2 on days 1 through 5 and days 8 through 12 every 28 days with (n = 246) or without (n = 246) bevacizumab at 5 mg/kg on days 1 and 15. Patients could have received up to two previous chemotherapy regimens for advanced disease. Treatment continued until disease progression or unacceptable toxicity. The primary endpoint was overall survival.
KEY POINTS
- The addition of bevacizumab to FTD-TPI prolonged overall survival in previously treated patients with metastatic colorectal cancer.
- Median overall survival was 10.8 vs 7.5 months.
Overall Survival
Median follow-up was 14.2 months (interquartile range [IQR] = 12.6–16.4 months) in the bevacizumab group and 13.6 months (IQR = 12.7–15.9 months) in the control group. Median overall survival was 10.8 months (95% confidence interval [CI] = 9.4–11.8 months) in the bevacizumab group vs 7.5 months (95% CI = 6.3–8.6 months) in the control group (hazard ratio [HR] = 0.61, 95% CI = 0.49–0.77, P < .001). Overall survival rates at 6 and 12 months were 77% vs 61% and 43% vs 30%, respectively.
Median progression-free survival was 5.6 months (95% CI = 4.5–5.9 months) in the bevacizumab group vs 2.4 months (95% CI = 2.1–3.2 months) in the control group (HR = 0.44, 95% CI = 0.36–0.54, P < .001). Progression-free survival rates at 6 and 12 months were 43% vs 16% and 16% vs 1%, respectively.
Median time to worsening of Eastern Cooperative Oncology Group score from 0 or 1 to ≥ 2 was 9.3 months (95% CI = 8.3–10.6 months) in the bevacizumab group vs 6.3 months (95% CI = 5.6–7.2 months) in the control group (HR = 0.54, 95% CI = 0.43–0.67).
Adverse Events
Grade ≥ 3 adverse events occurred in 72.4% of patients in the bevacizumab group vs 69.5% of the control group. The most common grade 3 or 4 adverse events were neutropenia in both groups (43.1% vs 32.1%). Adverse events of any grade that were more common in the bevacizumab group included hypertension (10.2% vs 2.0%; grade 3 or 4 in 5.7% vs 1.2%) and nausea (37.0% vs 27.2%). Adverse events led to discontinuation of treatment in 12.6% of patients in both groups. No treatment-related deaths occurred.
The investigators concluded, “Among patients with refractory metastatic colorectal cancer, treatment with FTD-TPI plus bevacizumab resulted in longer overall survival than FTD-TPI alone.”
Josep Tabernero, MD, PhD, of Vall d’Hebron Barcelona Hospital Campus and Institute of Oncology, Barcelona, is the corresponding author for The New England Journal of Medicine article.
Disclosure: The study was funded by Servier and Taiho Oncology. For full disclosures of the study authors, visit nejm.org.
