TKI Combination vs Monotherapy for Advanced Melanoma and the Risk for CV Adverse Events

Source: Dermatology Advisor, November 2019

Risks of high-grade arterial hypertension and high-grade reduction in left ventricular ejection fraction (LVEF) are increased for patients with advanced melanoma treated with a combination of BRAF and MEK inhibitors compared with those treated with BRAF inhibitor alone, according to study results published in JAMA Open Network.

Mutations in BRAF are common in melanoma, and are associated with increased tumor growth and proliferation through upregulation of the mitogen-activating protein kinase (MAPK) signaling pathway.

Results of randomized clinical trials of patients with advanced melanoma have demonstrated that dual targeting of the MAPK pathway with the combination of a BRAF inhibitor and a MEK inhibitor (eg, dabrafenib/trametinib, vemurafenib/cobimetinib, encorafenib/binimetinib) improved survival rates more effectively than did BRAF inhibitor therapy alone. Although increased risks of cardiovascular adverse events (CVAEs) with BRAF/MEK inhibitor combination therapy have been previously reported, these investigators stated that “the nature and incidence of CVAEs associated with BRAF and MEK inhibitor therapy are incompletely described.”

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