Detection of the BRAF V600E mutation has important genetic, prognostic, and therapeutic implications for patients with metastatic colorectal cancer (mCRC), as it aids in the identification of a subgroup of patients who derive little benefit from standard treatments and have an extremely poor prognosis. Secondary analyses of BRAF V600E-mutated subsets from multiple randomized clinical trials have demonstrated a lack of therapeutic benefit and poor prognosis with conventional cytotoxic chemotherapy doublets, highlighting the need for novel effective treatments for this subpopulation. In contrast to patients with BRAF V600E-mutated metastatic melanoma, only 5% of patients with BRAF V600E-mutated mCRC responded to BRAF inhibitor monotherapy in an early-phase trial. Basic science efforts to define resistance mechanisms to BRAF inhibition have generated new therapeutic approaches for these patients. As a result, the treatment landscape for mCRC with a BRAF V600E mutation has shifted dramatically in recent years. Promising clinical trials using combination therapies that inhibit the mitogen-activated protein kinase (MAPK) pathway and alternative active pathways have demonstrated major advances for patients with BRAF V600E-mutated mCRC.
Evolving Strategies for the Management of BRAF-Mutant Metastatic Colorectal Cancer
Stefania Napolitano;
2019
Abstract
Detection of the BRAF V600E mutation has important genetic, prognostic, and therapeutic implications for patients with metastatic colorectal cancer (mCRC), as it aids in the identification of a subgroup of patients who derive little benefit from standard treatments and have an extremely poor prognosis. Secondary analyses of BRAF V600E-mutated subsets from multiple randomized clinical trials have demonstrated a lack of therapeutic benefit and poor prognosis with conventional cytotoxic chemotherapy doublets, highlighting the need for novel effective treatments for this subpopulation. In contrast to patients with BRAF V600E-mutated metastatic melanoma, only 5% of patients with BRAF V600E-mutated mCRC responded to BRAF inhibitor monotherapy in an early-phase trial. Basic science efforts to define resistance mechanisms to BRAF inhibition have generated new therapeutic approaches for these patients. As a result, the treatment landscape for mCRC with a BRAF V600E mutation has shifted dramatically in recent years. Promising clinical trials using combination therapies that inhibit the mitogen-activated protein kinase (MAPK) pathway and alternative active pathways have demonstrated major advances for patients with BRAF V600E-mutated mCRC.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
