Abstract
Purpose: Poly ADP ribose polymerase (PARP) inhibitors can effectively kill cancer cells by restraining the activity of DNA repair enzymes and utilizing the characteristics of BRCA mutations. This article evaluates the efficacy and safety of PARP inhibitors (PARPis) in the maintenance treatment of ovarian cancer.Method: We searched for clinical trials in electronic databases. PARPis efficacy were evaluated by the hazard ratios (HR) and its 95% confidence intervals (95% CI) of overall survival (OS) and progression-free survival (PFS) between the PARPis groups and placebo groups, while the PARPis’ safety was assessed by relative risk (RR) values of adverse events (AEs) between the two arms.Results: The immature OS data manifested that patients with BRCA mutation receiving PARPis therapy versus placebo therapy appeared to have longer OS (HR = 0.78, 95%CI = 0.61–1.01; P = 0.06). Compared with placebo group, PARP group had a significant advantage in PFS in ovarian cancer patients with BRCA wild-type (BRCAwt), BRCA mutation (BRCAm), BRCA status unclassified, BRCA1 mutation subgroup and the BRCA2 mutation subgroup (BRCAwt: HR = 0.53, 95%CI = 0.42–0.68, P < 0.00001; BRCAm: HR = 0.30, 95%CI = 0.26–0.34, P < 0.00001; BRCA status unclassified: HR = 0.52, 95%CI = 0.41–0.66, P < 0.00001; BRCA1m: HR = 0.38, 95%CI = 0.29–0.48, P < 0.00001; BRCA2m: HR = 0.23, 95%CI = 0.10–0.57, P = 0.001). Our analysis revealed the incidence rates for AEs of grade ≥3 (grades 3 to 4) and serious AEs in PARPis group were 55.19% and 26.29%, respectively.Conclusion: Our meta-analysis demonstrates that PARPis therapy can significantly improve PFS in ovarian cancer patients, but it has no benefit in OS. However, the therapy is associated with a significant increase in the risk of AEs of grade ≥ 3 and serious AEs.
Highlights
Based on American cancer statistics in 2019, ovarian cancer is the 11th most common cancer, with approximately 22,530 newly diagnosed ovarian cancer cases, and the 5th leading cause of cancer-related death, with estimated 13,980 ovarian cancer deaths [1]
poly (adenosine diphosphate [ADP]–ribose) polymerase (PARP) group had a significant advantage in progression-free survival (PFS) in ovarian cancer patients with BRCA wild-type (BRCAwt), BRCA mutation (BRCAm), BRCA status unclassified, BRCA1 mutation subgroup and the BRCA2 mutation subgroup (BRCAwt: hazard ratios (HR) = 0.53, 95%95% confidence interval (CI) = 0.42–0.68, P < 0.00001; BRCAm: HR = 0.30, 95%CI = 0.26–0.34, P < 0.00001; BRCA status unclassified: HR = 0.52, 95%CI = 0.41–0.66, P < 0.00001; BRCA1m: HR = 0.38, 95%CI = 0.29–0.48, P < 0.00001; BRCA2m: HR = 0.23, 95%CI = 0.10–0.57, P = 0.001)
Our meta-analysis demonstrates that PARP inhibitors (PARPis) therapy can significantly improve PFS in ovarian cancer patients, but it has no benefit in overall survival (OS)
Summary
Based on American cancer statistics in 2019, ovarian cancer is the 11th most common cancer, with approximately 22,530 newly diagnosed ovarian cancer cases, and the 5th leading cause of cancer-related death, with estimated 13,980 ovarian cancer deaths [1]. Compared with mutation-negative patients, patients carrying BRCA mutations have an advantage in progression-free and overall survival, and more frequently. BRCA is known to be involved in homologous recombination [6–8], and the targeted inhibition of specific DNA repair pathways may provide an appropriate treatment for cancer [7]. BRCA-mutation positive epithelial ovarian cancer (EOC) patients appear impaired ability to repair double-stranded DNA breaks via homologous recombination, which may partly explain the molecular basis for heightened sensitivity to platinum and PARPis, as well as better survival compared with nonhereditary EOC patients [4,9–11]
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