New targeted agents directed against the RAS-RAF-MEK-ERK pathway show promising activity in early clinical development and particular interest is focused on selective inhibitors of mutant BRAF, which is present in one half of the cases of metastatic melanoma.
The significance of sarcoidal-type inflammation occurring during treatment of metastatic melanoma with a combination of BRAF and MEK inhibitors is unclear.
Combination of the BRAF inhibitor dabrafenib with the MEK inhibitor trametinib has significantly prolonged progression free survival compared to dabrafenib alone in metastatic melanoma.
Our review gives an overall point of view concerning BRAF and MEK pathways as well as the role of BRAF and MEK testing in directing the personalised treatment of patients with metastatic melanoma.
MEK inhibition is associated with improved response rate, progression-free survival, and overall survival in patients with BRAF-mutated metastatic melanoma.
Forty-two chemokine, cytokine, angiogenic, and growth factors were measured in the sera of 20 BRAF inhibitor-treated and four combination BRAF and MEK inhibitor-treated metastatic melanoma patients using a multiplex chemokine assay.
This first QOL assessment for a MEK inhibitor in metastatic melanoma demonstrated that trametinib was associated with less functional impairment, smaller declines in health status, and less exacerbation of symptoms versus chemotherapy.
We carried out a retrospective analysis of efficacy and safety in four patients with BRAF K601E and one patient with L597Q mutation-positive metastatic melanoma treated with the MEK inhibitor trametinib.
Studies presented or published during the European Society for Medical Oncology conference demonstrate that combining BRAF and MEK inhibitors improves progression-free and overall survival--and lowers the risk of resistance and toxicities--in patients with metastatic melanoma with BRAF V600E or V600K mutations.
Clinical observation of panniculitis in two patients with BRAF-mutated metastatic melanoma treated with a combination of a BRAF inhibitor and a MEK inhibitor.
We report a case of complete hematologic response of CML to MEK inhibition in a patient with synchronous metastatic melanoma, who received treatment with combination BRAF and MEK1/2 inhibitors.
With the advent of effective MAPK pathway inhibitors, including the US FDA-approved BRAF inhibitors vemurafenib and dabrafenib and MEK inhibitor trametinib, molecular analysis has become an integral part of the care of patients with metastatic melanoma.
Intrinsic and acquired resistance of metastatic melanoma to (V600E/K)BRAF and/or MEK inhibitors, which is often caused by activation of the PI3K/AKT survival pathway, represents a major clinical challenge.
The MEK inhibitor cobimetinib (Cotellic(®)) is indicated for the treatment of patients with BRAF (V600) mutation-positive unresectable or metastatic melanoma, in combination with the BRAF inhibitor vemurafenib (Zelboraf(®)).
Cobimetinib combined with vemurafenib is a new approved MEK inhibitor for first line treatment of metastatic melanoma patients with BRAF V600 mutations.
The BRAF inhibitor dabrafenib (Tafinlar(®)) and the MEK inhibitor trametinib (Mekinist(®)) are indicated, as monotherapy or in combination with each other, for the treatment of patients with unresectable or metastatic melanoma with a BRAF (V600) mutation.