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Ref Type Journal Article
PMID (36039514)
Authors Comito F, Aprile M, Pagani R, Siepe G, Sperandi F, Gruppioni E, Altimari A, De Biase D, Melotti B
Title Clinical characteristics and treatment outcomes of non-V600 E/K BRAF mutant melanoma patients: a single-institution experience.
Journal Vol Issue Date Pages Journal Short Title
Melanoma research 32 6 2022 Dec 01 477-484 Melanoma Res
URL
Abstract Text The widespread use of more sensitive detection tools, such as next-generation sequencing, has increased the identification of a variety of BRAF mutations other than V600E/K in melanoma patients. However, there is a lack of established data regarding the efficacy of BRAF/MEK inhibitors and immune-checkpoint immune inhibitors (ICI) for these patients. We performed a retrospective study, including all the patients diagnosed with stage III or IV melanoma that were referred to the University Hospital of Bologna from 2011 to 2021, carrying a non-V600E or V600K mutation of BRAF and who were started on systemic treatment. We found 14 patients with stage III or IV melanoma harboring the following BRAF mutations: V600R, V600_K601delinsE, K601E, p.T599_V600insT, L597V, G466R, S467L, and A598T. Of note, G466R and A598T BRAF mutations have never been previously reported in melanoma. Four patients received combined BRAF/MEK inhibitors, two patients BRAF inhibitor monotherapy, and six patients were treated with ICI for advanced melanoma; four patients received adjuvant treatment with nivolumab. Given the few cases and the absence of randomized clinical trials, it is important to report clinical experiences, which can guide physicians in the treatment of melanomas harboring rare BRAF mutations.

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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 predicted - sensitive Dabrafenib + Trametinib Case Reports/Case Series Actionable In a clinical case study, the combination of Mekinist (trametinib) and Tafinlar (dabrafenib) resulted in a partial response in one of two patients with melanoma harboring BRAF V600R, with a progression-free survival of 52.2 months in the responding patient (PMID: 36039514). 36039514