BRAF inhibitor [Neurosurgery Wiki]

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====== BRAF inhibitor ======

We have seen significant progress in the development of systemic therapies to treat patients with advanced melanoma. Use of these new treatment modalities, which include immune checkpoint inhibitors and small molecule [[BRAF inhibitor]]s, lead to increased overall survival and better outcomes. Although revolutionary, these therapies are often less effective against melanoma brain metastases, and frequently the CNS is the major site of treatment failure. The development of brain metastases remains a serious complication of advanced melanoma that is associated with significant morbidity and mortality. New approaches to both prevent the development of brain metastases and treat established disease are urgently needed
((Abate-Daga D, Ramello MC, Smalley I, Forsyth PA, Smalley KSM. The biology and 
therapeutic management of melanoma brain metastases. Biochem Pharmacol. 2017 Dec 
23. pii: S0006-2952(17)30731-1. doi: 10.1016/j.bcp.2017.12.019. [Epub ahead of
print] Review. PubMed PMID: 29278675.
)).

Landmark trials of BRAF inhibitors (BRAFi) and anti-PD-1 checkpoint inhibitor [[immunotherapy]] have shown high response rates and prolonged survival in patients with [[melanoma]], but have tended to exclude patients with central nervous system metastasis, particularly those with [[leptomeningeal metastases]] (Larkin, Hodi, & Wolchok, 2015; G. V. Long et al., 2014; Robert et al., 2015). Subsequent trials in those with parenchymal brain metastases have shown these agents have similar and often concordant responses to extracranial metastasis, but the activity in those with leptomeningeal metastases has not been adequately addressed in any prospective trial (Goldberg et al., 2016; Georgina V. Long et al., 2017; G. V. Long et al., 2012; Tawbi et al., 2017)
((Arasaratnam M, Hong A, Shivalingam B, Wheeler H, Guminksi AD, Long GV, Menzies
AM. Leptomeningeal melanoma - a case series in the era of modern systemic
therapy. Pigment Cell Melanoma Res. 2017 Oct 4. doi: 10.1111/pcmr.12652. [Epub
ahead of print] PubMed PMID: 28976629.
))