Despite the recent advances in the understanding of molecular and genetic etiopathogenesis of advanced melanoma and development of effective treatments, MBM remains a challenging disease and thorny management problem underscored by poor prognosis of MBM patients in multiple real-world reports.[149–152] ICI and targeted therapy have both led to significant improvements in the intracranial disease control. However, both treatment modalities carry the inherent risk of development of resistance and loss of response. The combination of ICI and targeted therapy has also been evaluated in a small number of clinical trials and has shown modest improvement in outcomes compared to either therapy alone. However, clinical trial data has also shown a significant amplification of toxicities with combination therapy which has led to limited adoption of this treatment model. Despite the current advances and the success of currently available therapies, sub-populations such as LMD and patients with progressive disease remain an extremely challenging population with relatively limited treatment options and poor outcomes. Novel treatments such as ACT have shown favorable outcomes in the heavily pre-treated population and remains an option for salvage treatment, despite the limitations associated with production and administration of engineered T-cells. MBM continues to be an area of immense research interest and multiple clinical trials are underway to evaluate combinations of various systemic agents, combined systemic and local therapy, and systemic agents and implantable devices. Further data is awaited to determine the most favorable combination of systemic and local therapies that can maximize the depth and length of response with minimum toxicities.
DD is supported by Melanoma Research Foundation Breakthrough Consortium (MRFBC), Gateway Foundation for Cancer Research (GFCR), Jack Buncher Foundation, and NIH/NCI awards including U01 CA271407, R01 CA257265 and P50 CA254865.
Provenance and Peer Review
This article was commissioned by the Guest Editors (Simon S. Lo, Balamurugan Vellayappan, Kevin Shiue and Jonathan P. S. Knisely) for the series "The Modern Approaches to the Management of Brain Metastases" published in Chinese Clinical Oncology. The article has undergone external peer review.
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Chin Clin Oncol. 2022;11(3):24 © 2022 AME Publishing Company