The efficacy and safety of poly ADP-ribose polymerase (PARP) inhibitors in patients with high-grade glioma (HGG): A systematic review and meta-analysis.

PURPOSE: While poly ADP-ribose polymerase (PARP) inhibitors represent a promising treatment strategy in early phase trials of patients with high-grade glioma (HGG), the clinical outcomes exhibit variability, mainly due to drug-specific pharmacokinetics and insufficient biological stratification involving MGMT and IDH status. We aimed to investigate the safety and efficacy of PARP inhibitors in grade 3 and 4 gliomas.

METHODS

A systematic review and data synthesis were conducted. Records were extracted from PubMed, Scopus, Web of Science, and Embase from inception to May 24th, 2025, and included in accordance with predetermined eligibility criteria.

RESULTS

Twelve studies, including 795 patients, were included. The pooled disease control rate (DCR) among patients with HGG was 27%; however, this estimate was associated with substantial heterogeneity and an extremely wide prediction interval (PI: 0.4-97.1%), indicating that the pooled value should not be interpreted as a stable estimate of expected clinical benefit in future studies or individual patient populations. The pooled grade ≥ 3 adverse event rate was 13% with a wide PI (2.2-51.2%), although heterogeneity was also substantial. Fixed-time survival outcomes and molecular/treatment subgroup analyses were summarized descriptively. Several subgroup findings, including those related to IDH status, MGMT promoter methylation, disease setting, and concomitant therapy, should be interpreted as exploratory because of limited study numbers, single-arm trial designs, inconsistent clinical contexts, and substantial between-study heterogeneity.

CONCLUSION

Available evidence suggests that PARP inhibitors have investigational activity and an overall acceptable safety profile in selected glioma populations, but the certainty of evidence is very low. Because pooled estimates were imprecise and accompanied by wide prediction intervals, these analyses should be regarded as descriptive and hypothesis-generating rather than clinically definitive. Larger randomized, biomarker-stratified trials with harmonized outcome definitions are required before PARP inhibitors can be assigned a clear therapeutic role in HGG.