Efficacy and safety of PARP inhibitors as the maintenance therapy in ovarian cancer: a meta-analysis of nine randomized controlled trials

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.

Keywords: Adverse events; BRCA; Efficacy and safety; Ovarian cancer; PARP inhibitors.

Figure 1. Flow diagram for selection of studies

Figure 2. Pooled HRs of OS comparing PARPis maintenance therapy arm with Placebo maintenance therapy arm in ovarian cancer patients with BRCAm (A) and BRCA status unclassified (B)

Figure 3. Pooled HRs of PFS comparing PARPis maintenance therapy arm with Placebo maintenance therapy arm in ovarian cancer patients with BRCAwt (A), BRCAm (B), BRCA status unclassified (C), BRCA1m (D) and BRCA2m (E)