Melanoma is characterized by oncogenic mutations in pathways regulating cell growth, proliferation, and metabolism. Greater than 80% of primary melanoma cases harbor aberrant activation of the mitogen-activated protein kinase kinase/extracellular-signal-regulated kinase (MEK/ERK) pathway, with oncogenic mutations in BRAF, most notably BRAF V600E, being the most common. Significant progress has been made in BRAF-mutant melanoma using BRAF and MEK inhibitors; however, non-V600 BRAF mutations remain a challenge with limited treatment options. We report the case of an individual diagnosed with stage III BRAF D594G-mutant melanoma who experienced an extraordinary response to the ERK1/2 inhibitor ulixertinib as fourth-line therapy. Ulixertinib was obtained via an intermediate expanded access protocol with unique flexibility to permit both single-agent and combination treatments, dose adjustments, breaks in treatment to undergo surgery, and long-term preventive treatment following surgical resection offering this patient the potential for curative treatment.
Published In/Presented At
Wolfe Z, Friedland JC, Ginn S, Blackham A, Demberger L, Horton M, McIntosh A, Sheikh H, Box J, Knoerzer D, Federowicz B, Stuhlmiller TJ, Shapiro M, Nair S. Case report: response to the ERK1/2 inhibitor ulixertinib in BRAF D594G cutaneous melanoma. Melanoma Res. 2022 May 12. doi: 10.1097/CMR.0000000000000830. Epub ahead of print. PMID: 35551160.
Medicine and Health Sciences
Department of Medicine, Hematology-Medical Oncology Division, Department of Pathology and Laboratory Medicine, Department of Radiation Oncology, Department of Surgery