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Melanoma Brain Metastases: An Update on the Use of Immune Checkpoint Inhibitors and Molecularly Targeted Agents
1Division of Medical Oncology, Department of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. stergios_moschos@med.unc.edu.
Abstract:
Brain metastases from melanoma are no longer uniformly associated with dismal outcomes. Impressive tumor tissue-based (craniotomy) translational research has consistently shown that distinct patient subgroups may have a favorable prognosis. This review provides a historical overview of the standard-of-care treatments until the early 2010s. It subsequently summarizes more recent advances in understanding the biology of melanoma brain metastases (MBMs) and treating patients with MBMs, mainly focusing upon prospective clinical trials of BRAF/MEK and PD-1/CTLA-4 inhibitors in patients with previously untreated MBMs. These additional systemic treatments have provided effective complementary treatment approaches and/or alternatives to radiation and craniotomy. The current role of radiation therapy, especially in conjunction with systemic therapies, is also discussed through the lens of various retrospective studies. The combined efficacy of systemic treatments with radiation has improved overall survival over the last 10 years and has sparked considerable research interest regarding optimal dosing and sequencing of radiation treatments with systemic treatments. Finally, the review describes ongoing clinical trials in patients with MBMs.
Insights
Melanoma brain metastases (MBMs) outcomes have improved with targeted therapies and immunotherapies. Advances in understanding MBM biology and clinical trials show better survival when combining systemic treatments with radiation.
Area of Science:
- Oncology
- Neuro-oncology
- Translational Research
Background:
- Melanoma brain metastases (MBMs) historically had poor prognoses.
- Tumor tissue analysis identified patient subgroups with favorable outcomes.
- Standard treatments before the 2010s included craniotomy and radiation therapy.
Purpose of the Study:
- To review historical treatments for MBMs.
- To summarize recent advances in MBM biology and treatment.
- To focus on clinical trials of targeted therapy and immunotherapy for MBMs.
Main Methods:
- Review of standard-of-care treatments up to the early 2010s.
- Summary of prospective clinical trials involving BRAF/MEK and PD-1/CTLA-4 inhibitors.
- Analysis of retrospective studies on radiation therapy in conjunction with systemic treatments.
Main Results:
- Systemic therapies (BRAF/MEK, PD-1/CTLA-4 inhibitors) offer effective complementary or alternative treatments to surgery and radiation.
- Combined systemic therapy and radiation have improved overall survival in the last decade.
- Significant research interest exists in optimizing the sequencing and dosing of combined treatments.
Conclusions:
- Melanoma brain metastases no longer carry uniformly dismal outcomes.
- Advances in systemic therapies and their combination with radiation have significantly improved patient survival.
- Ongoing clinical trials continue to explore optimal treatment strategies for MBMs.
