Efficacy of Veliparib Plus Temozolomide Combination Therapy in Cancer: A GRADE-Assessed Systematic Review and Meta-Analysis of Randomized Clinical Trials.

Abstract

Temozolomide (TMZ) is widely used in aggressive cancers, but its efficacy may be limited by tumor DNA repair mechanisms. Inhibition of PARP with veliparib (ABT-888) has been proposed to enhance TMZ-induced cytotoxicity. We conducted this systematic review and meta-analysis to evaluate the efficacy of this combination on overall survival (OS) and progression-free survival (PFS) in patients with cancer. PubMed, Scopus, CENTRAL, and ClinicalTrials.gov were systematically searched up to August 2026, using predefined terms. Eligible studies were phase II and III randomized controlled trials (RCTs) evaluating PFS and OS of veliparib combined with temozolomide versus control therapy. Random-effects models with restricted maximum-likelihood (REML) estimation with Hartung-Knapp (HK) adjustment were applied. Statistical analyses were performed with R with significance set at P<0.05. Certainty of evidence was assessed using the GRADE framework. From 729 records screened, 4 RCTs enrolling 1022 patients were included. No statistically significant improvement was shown in OS (HR=0.94, 95% CI: 0.78-1.13, I2=0.0) or PFS (HR=0.88, 95% CI: 0.71-1.08, I2=25.5). Subgroup analyses for OS similarly showed no statistically significant benefit. This meta-analysis did not demonstrate a statistically significant OS and PFS benefit from veliparib plus temozolomide compared with control therapy. This finding should be interpreted cautiously. The certainty of evidence was rated as moderate for both OS and PFS according to GRADE. Future studies should focus on biomarker-driven approaches and optimized dosing strategies to better define the clinical utility of this regimen.