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Ref Type Journal Article
PMID (27255157)
Authors Casadevall D, Vidal J, Gallardo F, Zuccarino F, Arumí-Uría M, Dalmases A, Bellosillo B, Montagut C
Title Dabrafenib in an elderly patient with metastatic melanoma and BRAF V600R mutation: a case report.
URL
Abstract Text Approximately 50 % of malignant melanomas harbor activating point mutations in the BRAF gene. Typically, these mutations result in the substitution of the amino acid valine at codon 600 of the gene, and 90-95 % of mutations are either BRAF (V600E) or BRAF (V600K). Specific BRAF inhibitors such as dabrafenib and vemurafenib are the mainstays of treatment in patients with metastatic BRAF-mutant malignant melanomas. The third most common BRAF mutation is V600R, which also leads to increased BRAF signaling. Although evidence exists about the activity of dabrafenib and vemurafenib in patients with the BRAF (V600R) mutation, these patients have been systematically excluded from recent trials with targeted therapies.Here, we report the positive results in terms of survival and quality of life obtained with dabrafenib in an 80-year-old Caucasian male patient with a Charlson Comorbidity Index of 8 diagnosed with metastatic malignant melanoma harboring the BRAF (V600R) mutation. Our patient was treated with dabrafenib for 7 months with minimal toxicity. We also report exploratory analyses of circulating tumor DNA during targeted treatment. Interestingly, the mutation was not detected after starting treatment and became detectable before radiological disease progression.Our report suggests that (1) a relevant benefit can be obtained with a BRAF inhibitor in real-world patients with a malignant melanoma harboring a BRAF (V600R) mutation, and that (2) circulating tumor DNA detection might be of help in assessing tumor burden in everyday clinical practice. The results reported here should encourage the inclusion of patients with BRAF (V600R)-mutated malignant melanomas in future prospective clinical trials with BRAF inhibitors.

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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
Drug Name Trade Name Synonyms Drug Classes Drug Description
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
BRAF V600R melanoma sensitive Dabrafenib Case Reports/Case Series Actionable In a clinical case study, a melanoma patient harboring BRAF V600R treated with Tafinlar (dabrafenib) demonstrated a reduction in lesion size after 2.5 months and at 5 months, stable disease, however, after 7 months progression ensued (PMID: 27255157). 27255157