Update on PARP inhibitors for the treatment of ovarian cancer.

Poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitors (PARPis) were first granted US Food and Drug Administration (FDA) approval for ovarian cancer. Trials have focused on high-grade serous histology, in which BRCA mutations and homologous recombination deficiency (HRD) are most common. The initial clinical trials of PARPis were performed in patients with heavily pretreated recurrent BRCA-mutated (BRCAm) ovarian cancer. Since then, concerns over possible reductions in overall survival with long-term PARPi treatment in recurrent disease have led to the withdrawal of most FDA approvals in this setting, and the use of PARPis has moved to the maintenance setting in newly diagnosed advanced ovarian cancer, in which trials have demonstrated significant progression-free survival benefits and trends for overall survival benefit with certain PARPis in patients who have BRCA mutations. Additionally, the risks of secondary acute myeloid leukemia and myelodysplastic syndrome are lower in the newly diagnosed setting than in the recurrent setting, potentially because of a predefined duration of PARPi treatment and/or less prior exposure to chemotherapy. Currently, several PARPis are FDA-approved in ovarian cancer: (1) olaparib (BRCAm), niraparib (BRCAm and BRCA wild-type [BRCAwt]), and olaparib/bevacizumab (BRCAm and BRCAwt/HRD) as maintenance therapy after platinum in newly diagnosed advanced disease; and (2) olaparib, niraparib, and rucaparib for recurrent BRCAm platinum-sensitive disease. This review discusses PARPi data in the newly diagnosed and recurrent settings, how current FDA approvals have evolved, and PARPi combination data.