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Ref Type
PMID (36686670)
Authors Zhang S, Yang Z, Cheng Y, Guo X, Liu C, Wang S, Zhang L
Title BRAF L485-P490 deletion mutant metastatic melanoma sensitive to BRAF and MEK inhibition: A case report and literature review.
Journal Vol Issue Date Pages Journal Short Title
Frontiers in pharmacology 13 2022 1019217 Front Pharmacol
URL
Abstract Text Background: The combination therapy of BRAF inhibitors (BRAFis) and MEK inhibitors (MEKis) has been approved as a first-line treatment for metastatic melanoma with BRAF V600 mutants. Recently, BRAF mutations have been divided into three subtypes based on biochemical and signaling characteristics. Unlike V600 mutants that show class I BRAF mutations, evidence of the effects of using BRAF inhibitors and MEK inhibitors in patients with non-V600 BRAF mutations remains unclear. The exploration of effective therapy for non-V600 BRAF mutations in melanoma has thus attracted much interest. Case presentation: We reported a case of a 64-year-old female metastatic melanoma patient with a novel BRAF p.L485-P490 deletion mutation. The patient received anti-PD1 agent pembrolizumab (100 mg) therapy as the first-line treatment for two cycles, which was terminated due to an intolerable adverse effect. Considering the p.L485-P490 deletion mutation signal as an active dimer which is akin to a class II BRAF mutation, the patient underwent dabrafenib and trametinib combination therapy as a second-line treatment. After two cycles of combination treatment, the patient achieved a partial response confirmed by radiological examinations. At the last follow-up date, the patient had obtained over 18 months of progression-free survival, and the treatment was well tolerated. Conclusion: The combination therapy of dabrafenib and trametinib has been proven to be an effective method as a later-line therapy for metastatic melanoma patients with class II BRAF in-frame deletion 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 L485_P490del melanoma predicted - sensitive Dabrafenib + Trametinib Case Reports/Case Series Actionable In a clinical case study, a patient with lymph node metastatic melanoma harboring BRAF L485_P490del and high CD274 (PD-L1) expression (TPS>=60%) experienced a partial response with regression of the target lesion after two cycles of second-line combination therapy with Tafinlar (dabrafenib) and Mekinist (trametinib), and at last follow up, demonstrated a sustained partial response and progression-free survival of at least 18 months (PMID: 36686670). 36686670