Clinical and radiological response of BRAF inhibition and MEK inhibition in patients with brain metastases from BRAF-mutated melanoma

Patients with brain metastases (BM) from melanoma have an overall survival (OS) of 2–6 months after whole-brain radiotherapy. Targeted therapy (TT) is an effective treatment for BRAF-mutated metastatic melanoma. Moreover, recent studies indicate intracranial responses of TT in patients with BM. We analyzed 146 patients with BM from BRAF-mutated melanoma treated with vemurafenib, dabrafenib, or dabrafenib+trametinib between 2010 and 2016. We determined clinical and radiological response, progression-free survival (PFS), and OS. Median OS of patients treated with dabrafenib+trametinib was 11.2 months [n=30; 95% confidence interval (CI): 6.8–15.7], 8.8 months for dabrafenib alone (n=31; 95% CI: 3.9–13.7), and 5.7 months for vemurafenib (n=85; 95% CI: 4.6–6.8). A significantly longer OS was observed in the dabrafenib+trametinib group than in the vemurafenib group (hazard ratio for death, 0.52; 95% CI: 0.30–0.89; P=0.02). Median intracranial PFS of all patients was 4.1 months. Median intracranial PFS for patients treated with dabrafenib+trametinib was 5.8 months (95% CI: 3.2–8.5), 5.7 months (95% CI: 3.0–8.4) for dabrafenib, and 3.6 months (95% CI: 3.5–3.8) for vemurafenib (P=0.54). A total of 63 (43%) patients had symptomatic BM. Intracranial disease control rate at 8 weeks in these patients was 65 versus 70% extracranially. Neurological symptoms improved in 46% of patients with symptomatic BM, whereas in 21%, they remained stable. Median OS in patients with BM from BRAF-mutated melanoma treated with dabrafenib+trametinib was significantly longer than for vemurafenib. Improvement of neurological symptoms was seen in almost half of the patients with symptomatic BM treated with TT. Correspondence to Dieta Brandsma, MD, PhD, Department of Neuro-Oncology, Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands Tel: +31 20 512 2570; fax: +31 20 512 2572; e-mail: d.brandsma@nki.nl Received August 13, 2017 Accepted December 15, 2017 Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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