Recent advances in our understanding of the molecular biology of epithelial
ovarian cancer have led to the development of a number of targeted therapies,
including poly-ADP-ribose polymerase (PARP) inhibitors. PARP inhibitors are a
novel class of therapeutic agents that target tumors with deficiencies in the
homologous recombination DNA repair pathway. Early studies have shown
significant efficacy for PARP inhibitors in patients with germline
BRCA1/2 mutations. It has become evident that
BRCA wild-type patients with other defects in the
homologous recombination repair pathway benefit from this therapeutic approach.
Importantly, companion homologous recombination deficiency scores are being
developed to help guide the selection of patients most likely to gain clinical
benefit from PARP inhibition. Olaparib, the first and most extensively
investigated PARP inhibitor, is now licensed in Europe for maintenance treatment
of patients with platinum-sensitive relapsed BRCA-mutated
(germline or somatic) high-grade serous ovarian cancer who have responded to
platinum-based chemotherapy. In the United States, olaparib is licensed for
treatment of patients with germline BRCA-mutated ovarian cancer
who have received 3 or more lines of chemotherapy. There are a number of other
PARP inhibitors in late phase clinical development in ovarian cancer including
rucaparib, niraparib, veliparib, and talazoparib. This review will focus on the
current evidence for PARP inhibitors in ovarian cancer and discuss ongoing
clinical trials and future research directions in this rapidly evolving
area.
