Mutations in BRCA1 and BRCA2 genes account for around 2-3% of breast cancer events and more than 10% of triple negative breast cancers. Olaparib (Lynparza®), an orally administered PARP inhibitor, demonstrated clinical benefit in a phase III trial for mutated BRCA-positive HER2 negative metastatic breast cancer. Areas covered: This review gives an overview of available preclinical and clinical data regarding olaparib, including its chemistry, mechanism of action, pharmacokinetics and pharmacodynamics, and evidence supporting antitumor efficacy and safety profile in breast cancer patients. Expert commentary: Olaparib improves progression-free survival in germline BRCA mutated HER2 negative metastatic breast cancer patients as compared to standard chemotherapy, with a manageable toxicity profile. Efficacy is of clinical relevance especially in the context of triple negative breast cancer. However, several aspects, such as sequencing or combination of these agents with other anticancer agents and identification of appropriate biomarkers, still need to be clearly defined.
Keywords: BRCA; Olaparib; OlympiAD trial; PARP inhibitors; breast cancer; synthetic lethality.