Patients diagnosed with melanoma brain metastasis (MBM) between 2010 and 2019 have had progressive improvement in overall survival (OS) compared with historic cohorts, and those diagnosed from 2015 to 2019 have had a longer OS than those diagnosed from 2010 to 2014, according to the results of a study published in Cancer.

Investigators sought to assess the use of multimodality, CNS-directed treatments and OS rates in patients with MBM, as advances such as precision-targeted therapies and immunotherapies over the last decade have led to improved survival for patients with advanced melanoma.

The retrospective study included 425 patients (72% men) with MBM who were treated at a single center from 2010 to 2019. Participants’ mean age at melanoma diagnosis was 56.6 years, and mean age at diagnosis of brain metastasis was 59.3 years.

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The cohort was diagnosed with 2488 MBMs, with 324 deaths occurring. Patients’ median OS was 8.9 months (95% CI, 7.9-11.3 months) from the diagnosis of brain metastasis, and the median follow-up was 22.5 months for survivors. Participants had a 3-year OS rate of 19.4% (95% CI, 15.5-24.1), and the 5-year OS rate was 13.6% (95% CI, 10.0-18.6).

Patients who were diagnosed with MBM between 2010 and 2014 had a median OS of 7.0 months (95% CI, 6.1-8.3 months), and those who were diagnosed between 2015 and 2019 had a median OS of 13.0 months (95% CI, 10.5-17.1 months).

Multivariable analysis found that the following were all statistically significantly associated with OS: number of brain metastases at diagnosis (hazard ratio [HR], 1.03; 95% CI, 1.01-1.04; P <.0001), year of MBM diagnosis (HR, 0.92; 95% CI, 0.87-0.97; P =.0008), leptomeningeal dissemination assessed as a time-dependent variable (HR, 3.63; 95% CI, 2.71-4.87; P <.0001), serum lactate dehydrogenase level greater than normal limit (HR, 2.14; 95% CI, 1.58-2.88; P <.0001), immunotherapy before a diagnosis of brain metastasis (HR, 1.40; 95% CI, 1.12-1.75; P =.003), and presence of extracranial disease (HR, 1.67; 95% CI, 1.07-2.60; P =.02).

At the last follow-up assessment, 326 patients (77%) had received immunotherapy, and 108 (25% of the total cohort; 52% of patients with BRAF mutations) had received BRAF-directed therapy.

Use of different CNS-directed treatment modalities was associated with presenting symptoms, diagnosis year, number and size of brain metastases, and extracranial disease. Patients who had undergone craniotomy had improved survival compared with those who did not (HR, 0.72; 95% CI, 0.56-0.93; P =.01).

The investigators noted that their study was not designed to assess whether immunotherapy and precision therapies decreased the rate or affected the timeline of development of brain metastasis in patients with advanced melanoma. Furthermore, the study did not compare the effectiveness of treatment paradigms, and the effects of BRAF/MEK inhibition were not assessed owing to the small subset of patients.

“Although immunotherapy and targeted therapies may elicit responses in MBM, these responses may not be as frequent or durable as those in the extracranial compartments,” the researchers commented. “It remains unclear whether the increase in OS in the age of targeted therapy and immunotherapy is caused by improved systemic or CNS disease control.”

Disclosures: Three of the study authors reported affiliations with pharmaceutical or medical technology-related companies.


Bander ED, Yuan M, Carnevale JA, et al. Melanoma brain metastasis presentation, treatment, and outcomes in the age of targeted and immunotherapies. Cancer. Published online March 2, 2021. doi:10.1002/cncr.33459