The novel combination therapy of PARP inhibitors and immune checkpoint inhibitors for ovarian cancer: a single-arm meta-analysis and systematic review

The use of PARP inhibitors in the maintenance therapy of various solid tumors is often limited by the development of PARP inhibitor resistance. Preclinical studies suggest that combining PARP inhibitors with immune checkpoint inhibitors could improve ovarian cancer outcomes and expand the range of patients eligible for treatment.Our aim was to evaluate the efficacy and safety of PARP inhibitor and ICI combination therapy for ovarian cancer, while also exploring how genetic variations, expression patterns, and platinum resistance affect its efficacy.A systematic search was conducted in CENTRAL, MEDLINE, and Embase from inception through August 14, 2024. Eligible studies included ovarian cancer patients treated with this combination therapy. Primary outcomes were objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and adverse events (AE), with results presented as rates or medians with 95% confidence intervals (CIs).Nine clinical studies were included, including data from 342 patients. The median PFS was 5.11 2.55–12.66 months. The ORR for best overall response varied by BRCA/HRD status, ranging from 48.44 21.63–76.17 % to 16 7.36–31.35 %. While direct comparisons were not possible, our findings suggest that platinum sensitivity, but not PD-L1 expression, may influence ORR. The rates of any-grade and serious adverse events were 95.59 3.29–100 % and 36.48 0.34–98.98 %, respectively.Despite limitations, our analysis indicates that combination therapy yields ORR and PFS similar to PARP inhibitor monotherapy. The combination may have the highest benefit for BRCA-mutated, platinum-sensitive ovarian cancer patients, with PD-L1 expression showing no impact on outcomes.