Efficacy and safety analysis of PARP inhibitors combined with drugs for
primary and relapsed ovarian cancer: A meta-analysis of randomized
controlled trials
Abstract
Background: Poly ADP-ribose polymerase (PARP) inhibitors have emerged as
maintenance therapy for advanced ovarian cancer. However, due to the
development of drug resistance, combination of PARP inhibitors with
other chemotherapeutic agents has become a contemporary research
hotspot. Methods: We conducted a meta-analysis of phase II or III
randomized controlled trials to analyze the efficacy and safety of
combinations of PARP inhibitors with various chemotherapeutic agents on
the progression-free survival (PFS) and overall survival (OS) of
patients with ovarian cancer. Results: A total of eight trials that
contained the combination of PARP inhibitors and chemotherapeutic agents
were included. Combination of PARP inhibitors with bevacizumab benefited
patients with BRCA mutations and HRD-positive status(HR=0.34 (95% Cl:
0.23–0.5; P<0.05); HR=0.35 (95% Cl: 0.27–0.45;
P<0.05)), while combination with chemotherapy prolonged the
PFS in the BRCA mutation, HRD, and homologous recombination proficiency
subgroups(HR=0.39 (95% Cl: 0.26–0.58; P<0.05);HR=0.57 (95%
Cl: 0.43–0.76; P<0.05); HR=0.79 (95% Cl: 0.64–0.98;
P<0.05) ). However, patients with BRCA wild-type or unknown
type benefited most from combination with cediranib. PARP inhibitors
increased the risk of G≥3 neutropenia when combined with
bevacizumab(RR=2.25, 95% Cl 1.09–4.62; P<0.05) and G≥3
anemia(RR=1.54, 95% Cl 1.16–2.05; P<0.05) and
neutropenia(RR=1.25,95% CL 1.00-1.57; P<0.05) when combined
with chemotherapy. Conclusion: Combination regimens of PARP inhibitors
showed benefits in both primary and recurrent ovarian cancer, and the
population subsets benefiting varied among different combinations. G≥3
adverse reactions were mainly hematological toxicities.