| General information |
| Database: | DB00049 |
| Objective: | Phase III TRIBE trial demonstrated that firstline FOLFOXIRI plus bev improved PFS and RECIST response and, at adjusted analyses, OS as compared to FOLFIRI plus bev. The prognostic and/or predictive effect to antiEGFRs of RAS and BRAF mutation is well established. They conducted this posthoc analysis in the TRIBE study in order to describe the predictive and prognostic effect of each molecular cathegory. |
| Authors: | Fotios Loupakis, et al |
| Title: | Subgroup analyses in RAS mutant, BRAF mutant and allwt mCRC pts treated with FOLFOXIRI plus bevacizumab (bev) or FOLFIRI plus bev in the TRIBE study |
| Journal: | J Clin Oncol |
| Year: | 2014 |
| PMID: | http://meeting.ascopubs.org/cgi/content/abstract/32/15_suppl/3519 maxtoshow=&hits=10&RESULTFORMAT=&searchid=1&FIRSTINDEX=10&minscore=5000&resourcetype=HWCIT |
| 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: | FOLFOXIRI + bevacizumab (bev) vs. FOLFIRI + bev |
| Study Type: | a phase III trial in subgroup analysis |
| Key Patients Feature: | RAS mutant, BRAF mutant and allwt mCRC pts |
| Biomarker: | AS mutant, BRAF mutant and allwt |
| Biomark Analysis: | KRAS, NRAS and BRAF were found mutated (mut) in 198 (52.8%), 20 (5.3%) and 28 (7.5%) cases, respectively. All wt patients were 129 (34.4%). |
| Control Group Info: | FOLFOXIRI + bevacizumab (bev) vs. FOLFIRI + bev in different subgroups types(All wt vs RAS mut vs BRAF mut) |
| Treatment Info: | Mutational analyses were centralized at the Coordinating Center. Mutations within KRAS and NRAS codon 12, 13 and 61 and BRAF codon 600 were analyzed by means of pyrosequencing in tumoral DNA extracted from primaries or metastases. Pts not bearing RAS or BRAFmutations were defined as ¡°all wt¡±. |
| Primary End Point: | PFS, OS |
| Secondary End Point: | NA |
| Patients Number: | 375 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | NA |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | FOLFIRI+bev:(All wt:11.3 ms; RAS mut: 9.5 ms; BRAF mut:5.5 ms); FOLFOXIRI+bev: (All wt:13.3 ms;RAS mut: 12.0 ms; BRAF mut:7.5 ms).No significant interaction between RAS or BRAF status and treatment effect was reported in PFS.All wt pts treated with upfront FOLFOXIRI plus bev achieved median PFS 13.3 ms.As compared to all wt pts, BRAF mut had significantly shorter PFS (HR: 2.29 [1.493.52], p=0.0002);for RASmut no difference in PFS was detected (HR: 1.15 [0.911.45], p=0.256) |
| Median OS A vs. C: | FOLFIRI+bev:(All wt:34.4 ms; RAS mut: 23.1 ms; BRAF mut:10.8 ms); FOLFOXIRI+bev: (All wt:41.7 ms;RAS mut: 28.6 ms; BRAF mut:19.1 ms).No significant interaction between RAS or BRAF status and treatment effect was reported. All wt pts treated with upfront FOLFOXIRI plus bev achieved median OS was 41.7 ms.As compared to all wt pts, BRAF mut had significantly shorter OS (HR: 3.31 [2.035.39], p<0.0001);for BRAF mutant OS was significantly shorter (HR: 1.48 [1.092.00], p=0.012). |
| Adverse Event(agent arm): | NA |
| Conclusions: | Benefit from FOLFOXIRI plus bev was independent of RAS and BRAF mutational status, with a trend toward a larger benefit in BRAF mut limited by small subgroup size. All wt pts treated with FOLFOXIRI plus bev achieved impressive PFS and OS results. Independently from the treatment received RAS or BRAF mut pts had shorter longterm survival. |