Critical reviews in oncology/hematology · 2025
Effectiveness and safety of PARP inhibitors in ovarian cancer: An umbrella review of systematic reviews and meta-analyses.
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Tzang Chih-Chen, Huang Ewen Shengyao, Wu Hui-Wen, Lin Wei-Chen, Lee Yi Ting, Luo Chiao-An, Chen Yan-Hua, Chang Zi-Yi, Chen Zi-Ting, Kuo Vicky Fu-Hsuan, Tzang Bor-Show, Hsu Tsai-Ching
Аннотация
BACKGROUND: Poly (ADP-ribose) polymerase inhibitors (PARPi) have become a key treatment for ovarian cancer, particularly in patients with BRCA mutations or homologous recombination deficiency (HRD).
METHODS: This umbrella review synthesizes findings from 35 systematic reviews and meta-analyses of randomized controlled trials to assess the efficacy and safety of PARPi in ovarian cancer.
RESULTS: Across studies, PARPi significantly improved progression-free survival, with the most pronounced benefit in BRCA-mutated and HRD-positive populations. Modest improvements in overall survival were also observed. Notably, although progression-free survival (PFS) benefits were seen even in BRCA wild-type and HRD-negative subgroups. While Olaparib, Niraparib, and Rucaparib demonstrated comparable efficacy, Veliparib showed less consistent outcomes. PARPi therapy was associated with increased risks of gastrointestinal and hematologic toxicities, including nausea, vomiting, neutropenia, and thrombocytopenia. Rare but serious risks, such as myelodysplastic syndrome, were also noted.
CONCLUSIONS: These findings support the continued use of PARPi as maintenance therapy in biomarker-selected ovarian cancer populations, while promoting the need for individualized risk-benefit assessment and further research into resistance mechanisms and predictive biomarkers.
METHODS: This umbrella review synthesizes findings from 35 systematic reviews and meta-analyses of randomized controlled trials to assess the efficacy and safety of PARPi in ovarian cancer.
RESULTS: Across studies, PARPi significantly improved progression-free survival, with the most pronounced benefit in BRCA-mutated and HRD-positive populations. Modest improvements in overall survival were also observed. Notably, although progression-free survival (PFS) benefits were seen even in BRCA wild-type and HRD-negative subgroups. While Olaparib, Niraparib, and Rucaparib demonstrated comparable efficacy, Veliparib showed less consistent outcomes. PARPi therapy was associated with increased risks of gastrointestinal and hematologic toxicities, including nausea, vomiting, neutropenia, and thrombocytopenia. Rare but serious risks, such as myelodysplastic syndrome, were also noted.
CONCLUSIONS: These findings support the continued use of PARPi as maintenance therapy in biomarker-selected ovarian cancer populations, while promoting the need for individualized risk-benefit assessment and further research into resistance mechanisms and predictive biomarkers.