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The role of systemic therapy in melanoma brain metastases: a narrative review
Kainat Saleem1, Diwakar Davar2
1Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
Background And Objective:
Melanoma is a disease notorious for the development of brain metastases, with consequently poor outcomes for patients who develop melanoma brain metastases (MBM). The treatment options for patients with MBM were limited to radiotherapy and surgery. MBM patients, particularly those with symptomatic disease, were excluded from clinical trials of immune checkpoint inhibitors (ICI) and BRAF/MEK inhibitors. Recent post-approval studies have, demonstrated important roles for existing systemic ICIs and BRAF/MEK inhibitors in untreated MBM, dramatically altering the landscape of melanoma patients in general and MBM in particular. These trials have also identified key areas for which more effective strategies are needed including: symptomatic MBM, and leptomeningeal disease (LMD).
Methods:
PubMed, Scopus and Embase databases were systematically queried to obtain records pertaining to the etiology of and treatment for MBM. Clinical trial databases were reviewed to obtain details regarding MBM clinical trials.
Key Content And Findings:
We discuss the etiopathogenesis of MBM and the novel immune, molecular and metabolic features of MBM that make this disease a unique therapeutic challenge. We review advances in systemic therapy with ICIs and BRAF/MEK inhibitors in untreated MBM, along with novel combinations. Finally, we debate challenging situations such as LMD, and delineate novel treatments and new paradigms for therapeutic interventions.
Conclusions:
The historically poor outcomes for MBM patients have been transformed with the advent of effective systemic therapies including ICIs and BRAF/MEK inhibitors. An improved understanding of the molecular and immunogenomic characterization of MBMs has provided new targets that are being exploited in the clinic.
Insights
Melanoma brain metastases (MBM) outcomes have improved with immune checkpoint inhibitors (ICI) and BRAF/MEK inhibitors. Further research is needed for symptomatic MBM and leptomeningeal disease (LMD).
Area of Science:
- Oncology
- Immunology
- Molecular Biology
Background:
- Melanoma brain metastases (MBM) historically have poor patient outcomes.
- Treatment options for MBM were previously limited to surgery and radiotherapy.
- MBM patients were often excluded from clinical trials of novel therapies.
Purpose of the Study:
- To review the etiopathogenesis and unique challenges of MBM.
- To discuss advances in systemic therapies for MBM, including immune checkpoint inhibitors (ICI) and BRAF/MEK inhibitors.
- To explore novel treatment strategies for challenging MBM situations like leptomeningeal disease (LMD).
Main Methods:
- Systematic literature search of PubMed, Scopus, and Embase databases for MBM etiology and treatment.
- Review of clinical trial databases for MBM-specific trial information.
Main Results:
- Systemic immune checkpoint inhibitors (ICI) and BRAF/MEK inhibitors show significant efficacy in untreated MBM.
- These therapies have dramatically altered the treatment landscape for melanoma patients with brain metastases.
- Key challenges remain, including symptomatic MBM and leptomeningeal disease (LMD).
Conclusions:
- Effective systemic therapies, including ICIs and BRAF/MEK inhibitors, have transformed outcomes for MBM patients.
- Understanding the molecular and immunogenomic characteristics of MBMs is crucial for developing new therapeutic targets.
- New treatment paradigms are emerging for complex MBM cases.
