Abstract
Until recently, there were few treatment options for patients with advanced or metastatic melanoma associated with significant increases in overall survival. Of these, patients with disease that has metastasized to the brain have a particularly poor prognosis and generally ineffective treatment options. Recent advances in immuno-oncology have led to the approval of ipilimumab, an antibody that blocks cytotoxic T-lymphocyte antigen-4 to augment antitumour T-cell responses, and vemurafenib, a BRAF kinase inhibitor. These agents, along with others on the horizon, are promising treatment options for patients with melanoma and CNS involvement. Here we review the data generated to date in patients with melanoma and brain metastases and suggest the direction that future studies may take to optimize outcomes in this subpopulation of patients.
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Financial & competing interests disclosure
JD Wolchok has recieved research funding from Bristol-Myers Squibb, GSK and Novartis and has consultancy and Speaker funding from Bristol-Myers Squibb, Merck and GSK. PA Ascierto has been a consultant for Merck Sharp & Dohme and Bristol Myers Squibb, has participated on advisory boards for Bristol Myers Squibb, Merck Sharp & Dohme, Roche-Genentech, Glaxo Smith Kline, Amgen, Medimmune, Celgene and Novartis. PA Ascierto has also received honoraria from Bristol Myers Squibb, Merck Sharp & Dohme and Roche-Genentech. O Hamid has recieved research funding from Genentech, Roche, GSK and BMS and Consultancy and Speaker funding from BMS and Genentech. K Margolin has recieved research funding from BMS, Merck, Roche-Genentech, GSK. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
The authors take full responsibility for the content of this publication and confirm that it reflects their viewpoint and medical expertise. The authors also wish to acknowledge StemScientific, funded by Bristol-Myers Squibb, for providing writing assistance and editorial support. Neither Bristol-Myers Squibb nor StemScientific influenced the content of the manuscript, nor did the authors receive financial compensation for authoring the manuscript.
Key issues
• Patients with melanoma that has metastasized to the brain have significantly worse progression-free survival, overall survival and overall prognosis than patients with no brain metastases and until recent years, few treatment options provided significant long-term survival potential for these patients.
• Stereotactic radiosurgery is frequently used and remains the standard of care; however, new immunotherapies are providing systemic options for many patients
• Data indicate that ipilimumab and BRAF-ihibiting drugs, like vemurafenib and dabrafenib, are associated with significant activity in patients with melanoma that has progressed to the brain with no unique or excessive toxicities.
• What remains unclear is the sequencing or possible combination of therapies that would optimize survival in patients while maintaining an acceptable safety profile.