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Sequential vs Combination Treatment With Fluoropyrimidines Plus Bevacizumab and Oxaliplatin for Metastatic Colorectal Cancer
Findings from the phase 3 C-cubed study favor sequential vs combination treatment with fluoropyrimidines plus bevacizumab and oxaliplatin for patients with metastatic colorectal cancer.
“In this trial, we tried to confirm whether the timing of oxaliplatin usage affects treatment duration. As oxaliplatin-containing therapies make discontinuation for any reason, including the lack of efficacy and intolerable toxicity, as are often annoying in the prevailing clinical practice,” wrote Ryo Inada, MD, Kochi Health Sciences Centre, Japan, and colleagues.
The C-cubed study enrolled 300 patients with previously untreated metastatic colorectal cancer. Patients were randomized in a 1:1 ratio to receive either sequential treatment of fluoropyrimidines with bevacizumab followed by the addition of oxaliplatin at first progression (n = 151), or combination treatment of fluoropyrimidines and oxaliplatin with bevacizumab (n = 149).
The primary end point of the study was time to failure of strategy (TFS). Secondary end points included overall survival (OS), progression-free survival (PFS), overall response rate (ORR), and safety.
The median TFS was 15.2 months (95% confidence interval [CI], 12.5 to 17.2 months) in the sequential treatment arm vs 7.8 months (95% CI, 6.3 to 9.5 months) in the combination arm (P <.001). Median OS was 27.5 months (95% CI, 24.4 to 32.7 months) vs 27 months (95% CI, 22.8 to 36 months), respectively (hazard ratio, 0.92; 95% CI, 0.66 to 1.28; P = .61). However; ORR was higher in the combination arm at 51.7% compared to 33.1% in the sequential arm.
“The findings support the extension of the sequential treatment starting from fluoropyrimidine plus bevacizumab to selected patients who do not need an objective response to the threatening disease,” concluded Dr Inada and colleagues.
Source:
Inada R, Nagasaka T, Shimokawa M, et al. Phase 3 trial of sequential versus combination treatment in colorectal cancer: The C-cubed study. Eur J Cancer. Published online: May 12, 2022. doi:10.1016/j.ejca.2022.04.009.
