BRAFV600E mutation status of involuting and stable nevi in dabrafenib therapy with or without trametinib

• Published in: JAMA dermatology (Chicago, Ill.) Vol. 150; no. 10; p. 1079
• Main Authors: McClenahan, Phil, Lin, Lynlee L, Tan, Jean-Marie, Flewell-Smith, Ross, Schaider, Helmut, Jagirdar, Kasturee, Atkinson, Victoria, Lambie, Duncan, Prow, Tarl W, Sturm, Richard A, Soyer, H Peter
• Format: Journal Article
• Language: English
• Published: United States 01.10.2014
• Subjects: Adult; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Dermoscopy; Humans; Imidazoles - administration & dosage; Male; Melanoma - drug therapy; Melanoma - secondary; Mutation; Nevus - drug therapy; Nevus - genetics; Nevus - pathology; Oximes - administration & dosage; Proto-Oncogene Proteins B-raf - genetics; Pyridones - administration & dosage; Pyrimidinones - administration & dosage; Skin Neoplasms - drug therapy; Skin Neoplasms - genetics; Skin Neoplasms - pathology
• ISSN: 2168-6084
• DOI: 10.1001/jamadermatol.2014.436

Recent advances in targeting BRAFV600E mutations, which occur in roughly 50% of melanomas and 70% of benign nevi, have improved response rates and survival in patients with melanoma. With increased survival, the importance of other comorbidities increases and requires consideration in long-term management. This case report discusses dynamic dermoscopic nevus changes that occur during dabrafenib therapy and offers some conclusions regarding BRAF mutations and the changes. A man in his 30s had been monitored with whole-body dermoscopy at roughly 7-month intervals as part of a nevus surveillance study. Fourteen months after his initial visit, metastases were found, and the patient entered a clinical trial of dabrafenib with or without trametinib therapy. Continued dermoscopic monitoring for the next 12 months revealed that approximately 50% of the existing acquired melanocytic nevi involuted, while the remaining nevi did not change. Biopsy findings from 1 unchanged and 1 involuted nevus showed BRAF wild type in the unchanged nevus, BRAFV600E mutation in the involuting nevus, and no malignant histopathologic characteristics in either one. Our observations indicate that a previously suggested hypothesis regarding involuting nevi in BRAF inhibitor therapy is correct: Nevi that involute while a patient is undergoing BRAF V600E inhibitor therapy possess the BRAF V600E mutation, while others that grow or remain unchanged are wild type. However larger-scale trials are required to gather conclusive data and create a more complete clinical picture.