Efficacy and safety of PARP inhibitors in the treatment of BRCA-mutated breast cancer: an updated systematic review and meta-analysis of randomized controlled trials

Abstract

ABSTRACT Introduction Poly-ADP-ribose polymerase inhibitors (PARPis) have emerged as a new class of therapeutic agents for breast cancer patients with breast cancer susceptibility gene (BRCA) mutations. However, the efficacy and toxicity of PARPis have not been clearly established. Methods This study comprehensively evaluated the efficacy and safety of PARPis in patients with BRCA-mutated breast cancer. Online databases were systematically searched, and six clinical trials were included. The primary endpoint of efficacy was progression-free survival (PFS), whereas the secondary endpoints were overall survival (OS) and objective response rate (ORR). Additionally, we assessed the safety of PARPis. Results The results of the meta-analysis showed that PARPis can effectively improve the PFS and OS in patients compared with the control group. The pooled HR (PARPi vs control groups) was 0.63 (95% CI, 0.55 − 0.73) and 0.83 (95% CI, 0.73 to −0.95) for PFS and OS, respectively. In safety, PARPis demonstrated controllable adverse reactions. There were no significant differences in overall AEs or grade ≥3 AEs between the PARP inhibitor and control arms. Conclusions Our results confirm the efficacy and safety of PARPis in patients with BRCA-mutated breast cancer, and more specifically clarify the efficacy of PARPis alone or in combination with other chemotherapy drugs.