In a patient-level meta-analysis reported in the Journal of Clinical Oncology, Chiara Cremolini, MD, PhD, and colleagues found that infusional fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI) plus bevacizumab was associated with significantly greater overall survival vs chemotherapy doublets plus bevacizumab as first-line treatment of patients with unresectable metastatic colorectal cancer.
Chiara Cremolini, MD, PhD
Study Details
The study included individual patient data from five trials (CHARTA, OLIVIA, STEAM, TRIBE, and TRIBE2) comparing FOLFOXIRI plus bevacizumab with chemotherapy doublets plus bevacizumab. The doublets consisted of infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX); fluorouracil, leucovorin, and irinotecan (FOLFIRI); irinotecan and capecitabine (XELIRI); or capecitabine and oxaliplatin (XELOX).
Key Findings
Data from 1,697 patients randomly assigned to receive FOLFOXIRI plus bevacizumab (n = 846) or doublets plus bevacizumab (n = 851) were included in the analysis. Median follow-up was 39.9 months.
Median overall survival was 28.9 months in the FOLFOXIRI group vs 24.5 months in the doublets group (hazard ratio [HR] = 0.81, 95% confidence interval [CI] = 0.72–0.91, P < .001). No significant heterogeneity among trials was observed (P = .39; I2 = 2%). No overall survival benefit of FOLFOXIRI plus bevacizumab was observed among the 9% of patients with BRAF-mutant tumors (HR = 1.11, 95% CI = 0.75–1.73).
Median progression-free survival was 12.2 months vs 9.9 months (HR = 0.74; 95% CI = 0.67–0.82, P < .001). Objective response rates were 64.5% vs 53.6% (P < .001). Among 139 vs 100 patients undergoing secondary surgery for metastases with radical curative intent, the R0 resection rates were 16.4% vs 11.8% (P = .007).
Patients in the FOLFOXIRI plus bevacizumab group had higher rates of grade 3 or 4 neutropenia (45.8% vs 21.5%, P < .001), febrile neutropenia (6.3% vs 3.7%, P = .019), nausea (5.5% vs 3.0%, P = .016), mucositis (5.1% vs 2.9%, P = .024), and diarrhea (17.8% vs 8.4%, P < .001). Death due to toxicity occurred in 2.3% vs 1.4% of patients (P = .277).
The investigators concluded, “FOLFOXIRI [plus] bevacizumab significantly and meaningfully improves survival of patients with metastatic colorectal cancer compared with doublets [plus] bevacizumab and provides advantage in progression-free survival, objective response rates, and R0 resection rate at the price of a moderate increase in toxicity. No increased benefit is observed among patients with BRAF-mutant tumors.”
Dr. Cremolini, of the Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: For full disclosures of the study authors, visit ascopubs.org.
