Cetuximab and Vemurafenib Plus FOLFIRI for BRAF V600E Mutated Advanced Colorectal Cancer (IMPROVEMENT)
Ontology highlight
ABSTRACT:
DISEASE(S): Colorectal Cancer,Colorectal Neoplasms
PROVIDER: 2288489 | ecrin-mdr-crc |
REPOSITORIES: ECRIN MDR
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Project description:BRAF mutation exists in about 10-12% of colorectal cancer, among which BRAF V600E mutation is the most common type, which is an important biomarker for predicting the prognosis and precise treatment efficacy of metastatic colorectal cancer (mCRC). The prognosis of metastatic colorectal cancer with BRAF V600E mutation is very poor, with OS of about 6-9 months. Previous studies have shown that single anti-BRAF inhibitor are ineffective, while multi-target inhibitions of Ras-Raf -MEK pathway is a possible effective strategy for BRAF V600E-mutant mCRC. Currently, the proven effective regimens include the VIC regimen (Vemurafenib + cetuximab + Irinotecan) and BEACON regimen (Encorafenib+ cetuximab +/- Binimetinib) from the SWOGS1406 study. Furthermore, BRAF inhibitor +MEK inhibitor combined with PD-1 monoclonal antibody has been shown to be an effective strategy in BRAF V600E-mutant malignant melanoma, which promote the study of the regimens for the treatment of BRAF V600E-mutant mCRC. Increasing basic and clinical studies have shown that cetuximab has ADCC effect, induces immunogenic cell death, promotes immune cell infiltration and other immunomodulatory effects, and has a synergistic effect with PD-1 monoclonal antibody in colorectal cancer. Based on those theories, we conducted the phase I study to explore the safety and preliminary efficacy of the regimen of Vemurafenib (BRAFi) plus cetuximab (EGFRi) combined with PD-1 monoclonal antibody in BRAF V600E-mutant /MSS type mCRC.
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