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Olaparib for the treatment of ovarian cancer

Introduction: Epithelial ovarian cancer (OC) remains the most lethal gynecologic malignancy. Germline mutations in either breast cancer gene 1(BRCA1) or BRCA2 genes are responsible for 15% of all OC, including those in women without a family history of cancer. Despite an initial response to the first line of treatment based on surgery and chemotherapy, most patients will relapse, highlighting the urgent need to develop smarter treatment options. The family of polyadenosine diphosphate-ribose polymerase (PARP) inhibitors is one of the most promising targeted agents. Areas covered: This report reviews the interest to target DNA repair defects with a focus on olaparib, the most investigated PARP inhibitor (PARPi) in OC. The results of the completed Phase I and II studies are analyzed and discussed with an update on translational research presented at major international congresses. Expert opinion: With five disparate histological subtypes, and a complex genomic landscape, OC remains a therapeutic challenge as evidenced by poor overall survival. Maturing data on olaparib provide evidence of efficacy and safety in the specific subgroup of women with high grade serous OC and BRCA mutations, and it seems likely that PARPi will represent an important step in the personalization of OC treatment.