Improved Overall Survival With FOLFOXIRI/Bevacizumab vs FOLFIRI/Bevacizumab in First-Line Treatment of Metastatic Colorectal Cancer
In an updated analysis of the Italian phase III TRIBE trial reported in The Lancet Oncology, Cremolini et al found that FOLFOXIRI (fluorouracil [5-FU], leucovorin, oxaliplatin, irinotecan) plus bevacizumab (Avastin) significantly prolonged overall survival in patients with unresectable metastatic colorectal cancer compared with FOLFIRI (5-FU, leucovorin, irinotecan) plus bevacizumab. The initial report from TRIBE showed prolongation of progression-free survival, the primary endpoint, with FOLFOXIRI/bevacizumab.
Study Details
In this open-label trial, 508 patients from 34 sites in Italy were randomly assigned between July 2008 and May 2011 to receive FOLFOXIRI/bevacizumab (n = 252) or FOLFIRI/bevacizumab (n = 256). Eastern Cooperative Oncology Group performance status had to be ≤ 2 in patients aged 18 to 70 years and 0 in those aged 71 to 75 years.
Bevacizumab was given as a 5-mg/kg intravenous dose. FOLFIRI consisted of irinotecan at 180 mg/m² via 60-minute infusion followed by leucovorin at 200 mg/m² via 120-minute infusion, a 400-mg/m² intravenous bolus of 5-FU, and continuous infusion of 5-FU at 2,400 mg/m² for 46 hours. FOLFOXIRI consisted of irinotecan at 165 mg/m² via 60-minute infusion followed by oxaliplatin at 85 mg/m² via intravenous infusion concurrently with leucovorin at 200 mg/m² via 120-minute infusion followed by continuous infusion of 5-FU at 3,200 mg/m² for 48 hours.
The current report includes analysis of overall survival, a secondary endpoint, and outcome in RAS and BRAF molecular subgroups.
Overall Survival
At a median follow-up of 48.1 months, median overall survival was 29.8 months (95% confidence interval [CI] = 26.0–34.3 months) in the FOLFOXIRI/bevacizumab group vs 25.8 months (95% CI = 22.5–29.1 months) in the FOLFIRI/bevacizumab group (hazard ratio [HR] = 0.80, P = .03). Second-line treatment was given to 76% of patients with progression in the FOLFOXIRI group and 76% of those with progression in the FOLFIRI group (P = .92), including oxaliplatin in 29% and 67% (P < .0001) and irinotecan in 63% and 31% (P < .0001).
Median overall survival was 37.1 months among patients with wild-type RAS and BRAF compared with 25.6 months in those with mutant RAS (HR = 1.49, 95% CI = 1.11–1.99) and 13.4 months in those with mutant BRAF (HR = 2.79, 95% CI = 1.75–4.46; likelihood-ratio test P < .0001). Treatment effect for overall survival was not significantly different across molecular subgroups (P = .52 for interaction).
The investigators concluded: “FOLFOXIRI plus bevacizumab is a feasible treatment option for those patients who meet the inclusion criteria of the present study, irrespective of baseline clinical characteristics and RAS or BRAF mutational status.”
Alfredo Falcone, MD, of University Hospital of Pisa, is the corresponding author for the Lancet Oncology article.
The study was funded by the Gruppo Oncologico del Nord Ovest (GONO) Cooperative Group and ARCO Foundation. For full disclosures of the study authors, visit www.thelancet.com/journals/lanonc.
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