Treatment of melanoma brain metastases

Goldinger, Simone M.; Panje, Cédric; Nathan, Paul

doi:10.1097/cco.0000000000000270

Cited by 13 publications

(10 citation statements)

References 60 publications

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“…Surgical resection is an option if the metastasis is solitary or limited in number and located in a surgically accessible area [ 141 ]. Surgery may be recommended if the metastasis is symptomatic and/or requires a diagnosis but biopsy of an alternative area is not feasible [ 142 , 143 , 144 ]. Immediate tumor de-bulking, definitive targeting of the lesion, and histological and molecular characterization of resected tissues, while alleviating symptomatic mass effects of the tumor, are all advantages of surgical resection.…”

Section: Melanoma Brain Metastasis Therapiesmentioning

confidence: 99%

Melanoma Brain Metastasis: Mechanisms, Models, and Medicine

Kircher

Silvis

Cho

et al. 2016

IJMS

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The development of brain metastases in patients with advanced stage melanoma is common, but the molecular mechanisms responsible for their development are poorly understood. Melanoma brain metastases cause significant morbidity and mortality and confer a poor prognosis; traditional therapies including whole brain radiation, stereotactic radiotherapy, or chemotherapy yield only modest increases in overall survival (OS) for these patients. While recently approved therapies have significantly improved OS in melanoma patients, only a small number of studies have investigated their efficacy in patients with brain metastases. Preliminary data suggest that some responses have been observed in intracranial lesions, which has sparked new clinical trials designed to evaluate the efficacy in melanoma patients with brain metastases. Simultaneously, recent advances in our understanding of the mechanisms of melanoma cell dissemination to the brain have revealed novel and potentially therapeutic targets. In this review, we provide an overview of newly discovered mechanisms of melanoma spread to the brain, discuss preclinical models that are being used to further our understanding of this deadly disease and provide an update of the current clinical trials for melanoma patients with brain metastases.

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Section: Melanoma Brain Metastasis Therapiesmentioning

confidence: 99%

Melanoma Brain Metastasis: Mechanisms, Models, and Medicine

Kircher

Silvis

Cho

et al. 2016

IJMS

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“…Among all cancers, melanoma is the third most common cause of brain metastasis (after lung and breast) [4]. Approximately 7% of patients with melanoma are found to have brain metastasis at diagnosis, and 40-50% of patients with stage IV melanoma develop brain metastases at some point in their disease course; indeed BRAF mutations may predispose patients to developing brain metastases [5,6]. Brain involvement is associated with poor prognosis, including an estimated 43% 3-month survival, as well as a high degree of morbidity and cost [7].…”

Section: Introductionmentioning

confidence: 99%

Clinical experience with combination BRAF/MEK inhibitors for melanoma with brain metastases: a real-life multicenter study

et al. 2019

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BRAF and MEK kinase inhibitors can be highly effective in treating BRAF-mutant melanomas, but their safety and activity in patients with active/symptomatic brain metastases are unclear. We sought to shed light on this open clinical question. We conducted a multicenter retrospective study on real-life patients with melanoma and active brain metastases treated with combination BRAF/MEK inhibitors. A total of 65 patients were included (38 men and 27 women; median age: 49 years). Of them, 53 patients received dabrafenib/trametinib, 10 received vemurafenib/cobimetinib, one received encorafenib/binimetinib, and one received vemurafenib/trametinib. We did not observe any unexpected treatment-related safety signals in our cohort. Overall, 17 patients continued on therapy through the cutoff date. After initiation of therapy, steroid dose could be decreased in 22 of 33 patients (11 tapered off entirely), anticonvulsants were stopped in four of 21, and narcotics were stopped in four of 12. Median progression-free survival from the start of therapy was 5.3 months (95% confidence interval: 3.6-6.1), and median overall survival was 9.5 months (95% confidence interval: 7.7-13.5). A total of 20 patients were surviving at the cutoff date. Univariate analysis of age, sex, ulceration status, thickness, stage, location, or lactate dehydrogenase did not reveal significant predictors of progression-free survival or overall survival within our cohort, but multivariate analysis suggested that older age, lower risk location of original lesion, and nodular melanoma are poor prognostic indicators. Combination therapy with BRAF/MEK inhibitors is a viable treatment option for patients with BRAF-mutant melanoma and brain metastases, but further studies should help to define the optimal treatment approach in this population.

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“…Five to twenty percent of patients with melanoma of any stage develop cerebral metastases (8). Five-year cumulative incidence of brain metastases was noted to be 7% for patients with all stages of melanoma.…”

Section: Discussionmentioning

confidence: 97%