TY - JOUR
T1 - Evolving strategies for the management of BRAF-mutant metastatic colorectal cancer
AU - Lee, Hey Min
AU - Morris, Van
AU - Napolitano, Stefania
AU - Kopetz, Scott
N1 - Publisher Copyright:
© 2019 ONCOLOGY (United States). All rights reserved.
PY - 2019/6
Y1 - 2019/6
N2 - 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.
AB - 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.
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M3 - Review article
C2 - 31219603
AN - SCOPUS:85068472719
SN - 0890-9091
VL - 33
SP - 206
EP - 211
JO - ONCOLOGY (United States)
JF - ONCOLOGY (United States)
IS - 6
ER -