RCC With Radio-Resistant Brain Metastases

Bradley G. Somer MD

Jul 21, 2015

Effective therapy that crosses the blood brain barrier is required. Additionally, XRT is unlikely to yield benefit as it seems radioresistant. Options for second line therapy include VEGFR inhibitor.  There seems to have been significant and rapid progression on Pazopanib, thus making a second VEGF inhibitor unlikely to yield major benefit. Alternative strategy is Everolimus. It has been shown to have the ability to cross the BBB  (O’Reilly T et al Cancer Chemother Pharmacol. 2010;65:625-639; Fox JH et al. Mol Neurodegener. 2010;5:26; Zhao H et al. Breast Ca Res Treat. 2012;131:425-436; Kwon CH et al. Proc Natl Acad Sci U S A. 2003;100:12923-12928). An alternative strategy is immunotherapy. There is more data on ipilumumab crossing the blood brain barrier in that the OR rate was similar in melanoma to the non-brain metastases CA184-042 and there are not much studies yet to answer the question of efficacy in the CNS with anti-PD1, anti-PDL1 therapy, but these are active study questions.