Clinical Efficacy of Immune Checkpoint Inhibitors in Glioblastoma and Brain Metastases
Maria Fioletova1, Alena Khalil1, Emma Baker2, Vito Evola1, Joshua Costin2, Samiksha Prasad2, Steven Vanni3, Regina Graham2
1Nova Southeastern University Dr. Kiran C. Patel College of Osteopathic Medicine, 2Nova Southeastern University Dr. Kiran C. Patel College of Allopathic Medicine, 3HCA Florida University Hospital
Objective:
To investigate existing clinical trial results on the use of ICIs against primary cancers and brain metastases from melanoma, non-small cell lung cancer (NSCLC), and breast cancer.
Background:
Brain tumors, including glioblastoma (GBM) and metastatic lesions, are highly aggressive, treatment-resistant, and have a poor prognosis. Immune checkpoint inhibitors (ICIs) are a type of immunotherapy that aids the patient’s immune system in killing cancer cells, often administered alongside other therapies in highly aggressive cancers.
Design/Methods:
A systematic review was conducted based on clinical trials evaluating ICIs for the treatment of GBM and brain metastases. An initial search of three electronic databases (Embase, Ovid MEDLINE, and Web of Science) identified 417 peer-reviewed articles. After applying the inclusion criteria and completing screening of Tier I (160 articles) and Tier II (12 articles), 7 studies were retained for final analysis. Eligible studies were English-language clinical trials published between 2015 and 2025 that enrolled adult participants (≥18 years), included a control arm, and reported results.
Results:
The analyzed studies evaluated overall survival (OS) and progression-free survival (PFS) in patients with newly diagnosed and recurrent GBM, including both MGMT-methylated and MGMT-unmethylated tumors. Treatment strategies included nivolumab as monotherapy or in combination with radiotherapy, temozolomide, or ipilimumab; ipilimumab with temozolomide. Across these studies, neither OS nor PFS improved compared with the respective control arms in GBM. The only trial to report a significant PFS extension used pembrolizumab in combination with pemetrexed and platinum chemotherapy in patients with NSCLC.
Conclusions:
ICIs offer a promising strategy for brain metastases, specifically NSCLC, enhancing immune activation and integrating well with multimodal treatments. However, GBM’s immunosuppressive microenvironment poses significant barriers, limiting ICI efficacy in larger trials. There were no significant changes in OS or PFS with ICI treatment for GBM. Further studies are warranted to define the role of ICIs in the management of brain metastases.
Disclaimer: Abstracts were not reviewed by Neurology® and do not reflect the views of Neurology® editors or staff.