In this initial experience of melanoma brain metastases treated with BRAF and MEK inhibition with stereotactic radiosurgery, we find that the two modalities can be combined safely. These outcomes should be assessed further in prospective evaluations.
Bindiya G. Patel, BS, Kamran A. Ahmed, MD, Peter A.S. Johnstone, MD, Hsiang-Hsuan Michael Yu, ScM, MD, Arnold B. Etame, MD, PhD; University of South Florida; H. Lee Moffitt Cancer Center and Research Institute
BACKGROUND: Brain metastases occur in at least one in three patients with advanced melanoma. The management of melanoma brain metastases continues to present challenges. Approximately 40% to 60% of patients with melanoma have an activating mutation in the BRAF gene, a serine-threonine protein kinase that leads to cell cycle activation and cellular proliferation modulated by the mitogen-activated protein kinase (MAPK) pathway. Use of a BRAF inhibitor (BRAFi) has shown improved extracranial and intracranial responses in the treatment of malignant melanoma. However, acquisition of therapeutic resistance remains a major limitation of BRAFi monotherapy in melanoma. The combined use of the BRAFi dabrafenib and the MEK inhibitor (MEKi) trametinib has been found to improve survival over use of dabrafenib alone. Synergies between targeted systemic therapies and radiation therapy offer potential for further investigation to improve intracranial response rates.
MATERIALS AND METHODS: In this study, we report our initial experience in the management of melanoma brain metastases with stereotactic radiosurgery (SRS) with the use of BRAFi and MEKi treatment. We identified six patients treated with SRS to 17 brain metastases within 3 months of BRAFi and MEKi administration. The median planning target volume was 0.42 cm3 (range: 0.02–1.29 cm3). The median treatment dose was 21 Gy (range: 18–24 Gy). The median follow-up of all lesions from SRS was 10.6 months (range: 5.8–28.5 mo).
RESULTS: One lesion was found to undergo local failure 21.7 months following SRS treatment. The median overall survival was 19.6 months (range: 6.1–31.8 mo) from the time of SRS treatment and 21.4 months (range: 12.1–30.9 mo) from the date of BRAFi and MEKi administration. There was no evidence of increased or unexpected toxicity with the two modalities combined.
CONCLUSIONS: In this initial experience of melanoma brain metastases treated with BRAF and MEK inhibition with SRS, we find that the two modalities can be combined safely. These outcomes should be assessed further in prospective evaluations.
Proceedings of the 98th Annual Meeting of the American Radium Society -americanradiumsociety.org