| General information |
| Database: | DB00992 |
| Objective: | In the TRIBE study, FOLFOXIRI (fluorouracil, leucovorin, oxaliplatin, and irinotecan) plus bevacizumab significantly improved progression free survival of patients with metastatic colorectal cancer compared with FOLFIRI (fluorouracil, leucovorin, and irinotecan) plus bevacizumab. In this updated analysis, they aimed to provide mature results for overall survivala secondary endpointand report treatment efficacy in RAS and BRAF molecular subgroups. |
| Authors: | Cremolini C, et al |
| Title: | FOLFOXIRI plus bevacizumab versus FOLFIRI plus bevacizumab as firstline treatment of patients with metastatic colorectal cancer: updated overall survival and molecular subgroup analyses of the openlabel, phase 3 TRIBE study. |
| Journal: | Lancet Oncol. |
| Year: | 2015 |
| PMID: | 26338525 |
| Trial Design |
| Clinical Trial Id: | NCT00719797 |
| Agent: | bevacizumab
|
| Target: | Vascular endothelial growth factor
|
| Cancer Type: | colorectal cancer |
| Cancer Subtype: | advanced colorectal cancer |
| Therapy Type: | com |
| Therapeutic Combination Type: | 2 |
| Therapeutic Combination Content: | FOLFIRI + bevacizumab or FOLFOXIRI + bevacizumab. |
| Study Type: | updated overall survival and molecular subgroup analyses of the openlabel, phase III TRIBE study |
| Key Patients Feature: | patients (aged 1870 years with Eastern Cooperative Oncology Group [ECOG] performance status of 2 or less and aged 7175 years with an ECOG performance status of 0) with unresectable metastatic colorectal cancer who were recruited from 34 Italian oncology units. |
| Biomarker: | Tissue samples for RAS and BRAF mutational status analyses |
| Biomark Analysis: | Median overall survival was 37.1 months (95% CI 29.742.7) in the RAS and BRAF wildtype subgroup compared with 25.6 months (22.428.6) in the RASmutationpositive subgroup (HR 1.49, 95% CI 1.111.99) and 13.4 months (8.224.1) in the BRAFmutationpositive subgroup (HR 2.79, 95% CI 1.754.46; likelihoodratio test p<0.0001). |
| Control Group Info: | FOLFIRI plus bevacizumab versus FOLFOXIRI plus bevacizumab |
| Treatment Info: | patients were randomly assigned (1:1) via a theybbased procedure to receive FOLFIRI plus bevacizumab or FOLFOXIRI plus bevacizumab. Bevacizumab was given as a 5 mg/kg intravenous dose. FOLFIRI consisted of a 180 mg/m(2) intravenous infusion of irinotecan for 60 min followed by a 200 mg/m(2) intravenous infusion of leucovorin for 120 min, a 400 mg/m(2) intravenous bolus of fluorouracil, and a 2400 mg/m(2) continuous infusion of fluorouracil for 46 h. FOLFOXIRI consisted of a 165 mg/m(2) intravenous infusion of irinotecan for 60 min, followed by an 85 mg/m(2) intravenous infusion of oxaliplatin given concurrently with 200 mg/m(2) leucovorin for 120 min, followed by a 3200 mg/m(2) continuous infusion of fluorouracil for 48 h. |
| Primary End Point: | overall survival in the main cohort and treatment efficacy in RAS and BRAF molecular subgroups |
| Secondary End Point: | NA |
| Patients Number: | 508 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | NA |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | 12.3 months (95% CI 11.0-13.3) in the FOLFOXIRI plus bevacizumab group compared with 9.7 months (9.2-10.9) in the FOLFIRI plus bevacizumab group (HR 0.77, 95% CI 0.65-0.93; p=0.006). |
| Median OS A vs. C: | 29.8 months (95% CI 26.034.3) in the FOLFOXIRI plus bevacizumab group compared with 25.8 months (22.529.1) in the FOLFIRI plus bevacizumab group (hazard ratio [HR] 0.80, 95% CI 0.650.98; p=0.03). 37.1 months (95% CI 29.742.7) in the RAS and BRAF wildtype subgroup compared with 25.6 months (22.428.6) in the RASmutationpositive subgroup (HR 1.49, 95% CI 1.111.99) and 13.4 months (8.224.1) in the BRAFmutationpositive subgroup (HR 2.79, 95% CI 1.754.46; likelihoodratio test p<0.0001). |
| Adverse Event(agent arm): | NA |
| Conclusions: | 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. |