(Open access funding provided by Semmelweis University)
Ovarian cancer is the eighth leading cause of cancer-related death among women, characterized
by late diagnosis and a high relapse rate. In randomized controlled trials, we aimed
to evaluate the efficacy and safety of PARP inhibitors (PARPi) in treating advanced
ovarian cancer.This review was registered on PROSPERO (CRD42021283150), included all
phase II and phase III randomized controlled trials (RCTs) assessing the effect of
PARPi on ovarian cancer until the 13th of April, 2022. The main outcomes were progression-
free survival (PFS), overall survival (OS), and adverse events (AEs). Pooled hazard
ratios (HRs), and risk ratios (RRs) were calculated with 95% confidence intervals
(95% CI). The random-effects model was applied in all analyses.In the meta-analysis,
16 eligible RCTs were included, with a total of 5,815 patients. In recurrent ovarian
cancer, PARPi maintenance therapy showed a significant PFS benefit over placebo in
the total population (HR 0.34, CI 0.29-0.40), BRCA mutant (HR 0.24, CI 0.18-0.31),
germline BRCA mutant (HR 0.23, CI 0.18-0.30), and BRCA wild-type cases (HR 0.50, CI
0.39-0.65). PARPi monotherapy also improved PFS (HR 0.62, CI 0.51-0.76) compared with
chemotherapy in BRCAm patients with recurrent ovarian cancer. The use of PARPi maintenance
therapy resulted in an improvement in PFS over placebo in newly-diagnosed cancers
in the overall population (HR 0.46, CI 0.30-0.71) and the BRCAm population (HR 0.36,
CI 0.29-0.44). Although the risk of severe AEs was increased by PARPi therapy compared
to placebo in most settings investigated, these side effects were controllable with
dose modification, and treatment discontinuation was required in the minority of cases.PARPis
are an effective therapeutic option for newly-diagnosed and recurrent ovarian cancer.
Despite a minor increase in the frequency of serious adverse effects, they are generally
well tolerated.
