Introduction: Poly (ADP-ribose) polymerase (PARP) inhibitors have demonstrated significant anticancer activity in cancers harboring homologous recombination deficiency (HRD), exemplified by high grade serous ovarian cancer (HGSC). PARP inhibitors (PARPi) are being used in women with newly diagnosed ovarian cancer as well as in the recurrent setting. PARPi combination therapies are in development.
Areas covered: This review discusses the treatment of ovarian cancer, key PARPi clinical trials, mechanisms of action of PARPi, and novel PARPi combination regimens under investigation. PubMed and ClinicalTrials.gov were searched for PARPi trials. Active development was confirmed via PharmaProjects.
Expert opinion: PARPi have shown to improve progression-free survival (PFS) for women with HGSC as monotherapy in both frontline and recurrent maintenance settings and as monotherapy as treatment for recurrence. These benefits are greatest in HGSC with underlying HRD, in particular for those with deleterious BRCA mutations, and with the least benefit in cancers that are HR proficient (HRP) and BRCA wild-type (wt). Thus far, an improvement in overall survival has only been demonstrated in patients with BRCA mutated EOC treated with olaparib maintenance in the platinum sensitive recurrence setting. Novel combinations of PARPi are undergoing testing in an effort to increase PARPi efficacy in HRP or PARPi-resistant cancers.
Keywords: BRCA; DNA damage; PARP inhibitor; homologous recombination; niraparib; olaparib; ovarian cancer; rucaparib; veliparib.