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| Ref Type | Journal Article | ||||||||||||
| PMID | (40411977) | ||||||||||||
| Authors | Bloem M, Suijkerbuijk KPM, Aarts MJB, van den Berkmortel FWPJ, Blank CU, Blokx WAM, Boers-Sonderen MJ, Boreel CDM, de Groot JWB, Haanen JBAG, Hospers GAP, Kapiteijn E, van Not OJ, Piersma D, Rikhof B, Stevense-den Boer AM, van der Veldt AAM, Vreugdenhil G, Wouters MWJM, van den Eertwegh AJM | ||||||||||||
| Title | Efficacy of encorafenib plus binimetinib in patients with BRAF-mutated melanoma brain metastases: Results from the Dutch Melanoma Treatment Registry. | ||||||||||||
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| Abstract Text | Data on the effectiveness of encorafenib/binimetinib in melanoma patients with brain metastases (BMs) are limited.All patients with BRAF V600-mutated melanoma and BMs treated with encorafenib/binimetinib between 2019 and 2022 in the Netherlands were included from the nationwide Dutch Melanoma Treatment Registry. Patients previously treated with other BRAF/MEK inhibitors were excluded. We analyzed objective response rates (ORR), progression-free survival (PFS), and overall survival (OS). Multivariable Cox regression identified factors associated with survival. Subgroup analyses included asymptomatic versus symptomatic BMs and line of treatment (first-line versus later-line).In total, 190 patients were included. Symptomatic BMs were present in 63 % of patients. Encorafenib/binimetinib was the first-line treatment in 64 % of all patients, while 36 % had prior immunotherapy. Overall, the ORR was 69.4 %, median PFS was 5.5 months (95 %CI 4.9-6.2), and median OS 11.9 months (95 %CI 10.0-15.7). Age ≥ 70, ECOG PS ≥ 2, symptomatic BMs, and elevated LDH were significantly associated with worse survival. Patients with prior immunotherapy had a median PFS of 6.9 months (95 %CI 4.3-9.6) and OS of 17.9 months (95 %CI 13.7-31.2), while this was 4.9 months (95 %CI 4.3-5.5) and 10.1 months (95 %CI 8.1-13.0) in treatment-naïve patients. Median PFS and OS in patients with asymptomatic versus symptomatic BMs were 6.1 months (95 %CI 4.9-9.8) and 20.5 (95 %CI 14.0-NA) versus 5.3 months (95 %CI 4.9-6.3) and 10.7 (95 %CI 8.9-13.7), respectively.Encorafenib/binimetinib has clinical activity in real-world melanoma patients with BMs. Their prognosis is determined by the presence of symptomatic BMs, age, ECOG PS, and LDH levels. | ||||||||||||
| Molecular Profile | Treatment Approach |
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| Gene Name | Source | Synonyms | Protein Domains | Gene Description | Gene Role |
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| Therapy Name | Drugs | Efficacy Evidence | Clinical Trials |
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| Drug Name | Trade Name | Synonyms | Drug Classes | Drug Description |
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| Gene | Variant | Impact | Protein Effect | Variant Description | Associated with drug Resistance |
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| Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
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| BRAF V600X | melanoma | predicted - sensitive | Binimetinib + Encorafenib | Clinical Study | Actionable | In a retrospective analysis, real-world treatment with the combination of Mektovi (binimetinib) and Braftovi (encorafenib) demonstrated activity in melanoma patients with brain metastases harboring a BRAF V600 mutation, with an objective response rate of 69.4% (125/180, 4 complete and 121 partial responses), median progression-free survival of 5.5 months, and median overall survival of 11.9 months (PMID: 40411977). | 40411977 |