However, recent breakthroughs have brought new hopes for patients and providers.While targeted therapy with BRAF and MEK inhibitors represents an important cornerstone in the treatment of metastatic melanoma, this chapter carefully reviews the past and current therapy options available, with a significant focus on immunotherapy-based approaches.
All MM cases (excluding ocular MM, n = 837) diagnosed in three non-consecutive years marked by major changes in the first-line treatments (2012: interleukin-2 and BRAF inhibitors; 2014: anti-CTLA-4: Cytotoxic T-Lymphocyte Antigen 4 and 2016: anti-PD-1: programmed cell death protein 1 and MEK inhibitors) were retrieved.
Targeted therapy with BRAF inhibitors (BRAFi) and MEK inhibitors (MEKi) provides rapid disease control with high response rates in patients with BRAF-mutant metastatic melanoma.
In this retrospective multicenter study with 60 patients suffering from inoperable or metastatic melanoma we evaluated the efficacy of re-challenge with a BRAF inhibitor (BRAF2) with or without MEK-inhibition after progressive disease upon previous treatment with a BRAF inhibitor (BRAF1) with or without MEK inhibition.
This analysis aimed to increase understanding of the role of baseline genetic features in the variability of response to BRAF and MEK inhibitor therapy for <i>BRAF</i><sup>V600</sup>-mutated 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.
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.
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(®)).
Although cAMP elevation did not alter the sensitivity of metastatic melanoma cells to BRAF(V600E) and MEK inhibitors, the EPAC-RAP1 axis appears to contribute to resistance to MAPK pathway inhibition.
In light of this, an indirect treatment comparison was performed between two BRAF/MEK inhibitor combination therapies for metastatic melanoma, dabrafenib plus trametinib and vemurafenib plus cobimetinib, in order to understand the relative efficacy and toxicity profiles of these therapies.
Combination therapy with BRAF and MEK inhibitors dramatically improves response rates, progression-free survival and overall survival in patients with BRAF-mutant metastatic melanoma compared to historical treatments such as chemotherapy.
The significance of sarcoidal-type inflammation occurring during treatment of metastatic melanoma with a combination of BRAF and MEK inhibitors is unclear.
BRAF and MEK inhibitors (BRAFi and MEKi) are actively used for the treatment of metastatic melanoma in patients with BRAF<sup>V600E</sup> mutation in their tumors.
Dual inhibition of the mitogen-activated protein kinase pathway with BRAF/MEK inhibitor (BRAFi/MEKi) therapy is a standard treatment for BRAFV600-mutant metastatic melanoma and has historically been associated with grade III pyrexia or photosensitivity depending on the combination used.
The introduction of targeted therapies including BRAF and MEK inhibitors as well as CTLA-4 and PD-1 axis targeting immune checkpoint inhibitors have dramatically improved the treatment and prognosis of patients with extracranial metastatic melanoma.
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.
Clinical observation of panniculitis in two patients with BRAF-mutated metastatic melanoma treated with a combination of a BRAF inhibitor and a MEK inhibitor.
Targeted therapy with BRAF plus MEK inhibitors has become the standard of care for patients with advanced-stage <i>BRAF</i> V600-mutant metastatic melanoma.
Targeted BRAF inhibition (BRAFi) and combined BRAF and MEK inhibition (BRAFi and MEKi) therapies have markedly improved the clinical outcomes of patients with metastatic melanoma.
Combined treatment of metastatic melanoma with BRAF and MEK inhibitors has improved survival, but the emergence of resistance represents an important clinical challenge.