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Immune Checkpoint Inhibitors in Glioblastoma IDHwt Treatment: A Systematic Review
Archit Bharathwaj Baskaran1, Olivia A Kozel2, Omkar Venkatesh3
1Department of Neurology, The University of Chicago, Chicago, IL 60637, USA.
Purpose:
A glioblastoma (GBM) is a primary brain tumor with significant unmet therapeutic needs. Immune checkpoint inhibitors (ICIs) have marked therapeutic benefits in many different cancers but have yet to show benefit for most GBM patients in phase III trials.
Methods:
A systematic review querying ClinicalTrials.gov for prospective clinical trials investigating ICI in GBM between 1950 and July 2024 was performed. Search terms comprised 11 distinct ICIs. Data abstracted include clinical trial NCT numbers with study titles and status, enrollment information, interventions, and more. Clinical trial identifying information, interventions, and outcomes were extracted.
Results:
One hundred and seventeen clinical trials were identified; four were phase 3. Most involved PD-1 or CTLA-4 blockade as monotherapy or in combination with standard-of-care. The large, randomized trials included CHECKMATE 143, CHECKMATE 498, CHECKMATE 548, and NRG BN007. These showed no improvement in median overall survival or progression-free survival in unselected patients. Biomarker-directed analyses suggest that a subset of GBM patients may benefit.
Conclusions:
ICI for the treatment of GBM has not demonstrated clear evidence of efficacy thus far. This review serves as a quick reference of ICI trial results in GBM. Biomarker-driven patient selection and/or novel approaches to overcome resistance mechanisms remain areas of viable inquiry.
