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Immune Checkpoint Inhibitors for Brain Metastases: A Primer for Neurosurgeons
Elisa Aquilanti1,2,3,4,5, Priscilla K Brastianos1,2,4,5
1Division of Hematology/Oncology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
Abstract:
Immune checkpoint inhibitors enhance immune recognition of tumors by interfering with the cytotoxic T-lymphocyte-associated antigen 4 (CTLA4) and programmed death 1 (PD1) pathways. In the past decade, these agents brought significant improvements to the prognostic outlook of patients with metastatic cancers. Recent data from retrospective analyses and a few prospective studies suggest that checkpoint inhibitors have activity against brain metastases from melanoma and nonsmall cell lung cancer, as single agents or in combination with radiotherapy. Some studies reported intracranial response rates that were comparable with systemic ones. In this review, we provide a comprehensive summary of clinical data supporting the use of anti-CTLA4 and anti-PD1 agents in brain metastases. We also touch upon specific considerations on the assessment of intracranial responses in patients and immunotherapy-specific toxicities. We conclude that a subset of patients with brain metastases benefit from the addition of checkpoint inhibitors to standard of care therapeutic modalities, including radiotherapy and surgery.
Insights
Immune checkpoint inhibitors targeting CTLA4 and PD1 pathways show promise for brain metastases in melanoma and lung cancer. These treatments, often combined with radiotherapy, offer improved outcomes for a subset of patients.
Area of Science:
- Oncology
- Immunology
- Neurology
Background:
- Immune checkpoint inhibitors (ICIs) like anti-CTLA4 and anti-PD1 therapies have revolutionized cancer treatment.
- These agents enhance anti-tumor immune responses by modulating T-cell activity.
Purpose of the Study:
- To review clinical data on the efficacy of ICIs in patients with brain metastases.
- To discuss considerations for assessing intracranial responses and managing immunotherapy-related toxicities.
Main Methods:
- Comprehensive literature review of studies investigating ICIs in brain metastases.
- Analysis of retrospective and prospective data on melanoma and non-small cell lung cancer brain metastases.
Main Results:
- ICIs demonstrate activity against brain metastases, with some studies reporting intracranial response rates comparable to systemic responses.
- Combination therapy with radiotherapy shows potential for enhanced efficacy.
Conclusions:
- A subset of patients with brain metastases can benefit from the addition of ICIs to standard treatments like radiotherapy and surgery.
- Further research is warranted to optimize ICI use and management in this patient population.
