The changing paradigm of management in melanoma brain metastases

Improved systemic treatment has improved the prognosis of metastatic melanoma (MM). However, brain metastases (BMs) are a frequent complication. We aimed to explore the outcome of these patients with modern therapeutic options.

We retrospectively analyzed 142 patients diagnosed with BM from MM at two institutions in Brisbane, Queensland, Australia during 2009-2016. Basic clinico-pathological parameters, treatments used and mortality data were collected.

With a median follow-up of 8 months, 115 patients had died, 112 from MM and 99 from neurologic death. Management included ablative therapy (n = 8), ablative therapy with targeted/immunotherapy (n = 54), targeted/immunotherapy (n = 55) and whole-brain radiotherapy/best supportive care (n = 25). The median overall survival (OS) was 8 (6.9-9.1) months. Statistically improved OS was found with the use of ablative techniques and BRAF/MEK tyrosine kinase inhibitor (TKI) post diagnosis of BM. In BRAF mutant patients (n = 117) who were TKI naïve at diagnosis of BM (n = 60), the median OS was 9 (6.2-11.8) months versus 5 (1.1-8.9) months in patients who developed BM on TKI treatment (P = 0.001). A complete intracranial response rate occurred in 12% of patients who had immunotherapy (n = 65) with all but two patients receiving stereotactic radiosurgery and no deaths have occurred in this group.

The outcomes of those with BM remain poor, particularly of those with BRAF mutant MM who fail TKI therapy with new BM. Most patients present with multiple BM and death is frequently due to neurological progressive disease. The use of ablative techniques and TKI use confers a longer OS in selected patients.