Study of Neoadjuvant Olaparib Monotherapy and Olaparib and Durvalumab Combination in HER2 Negative BRCAm Breast Cancer

The investigation of olaparib as monotherapy or olaparib in combination with durvalumab in patients with early stage BRCAm, oestrogen receptor (ER)-negative or ER-low, human epidermal growth factor receptor 2 (HER2)-negative breast cancer who are candidates for neoadjuvant therapy supports the ongoing effort to identify novel agents and new drug combinations that can improve pathological complete response (pCR) rates and event-free survival (EFS). In patients at a lower risk (T1b-c/N0) of disease recurrence and a higher chance for cure, monotherapy olaparib may provide adequate neoadjuvant treatment. In contrast, monotherapy olaparib may be inadequate neoadjuvant treatment for those patients at a higher risk (T2/N0 or T1/N1) of recurrence, and the addition of an immune checkpoint inhibitor (ICI) to the neoadjuvant regimen may improve long-term outcomes as was seen in KEYNOTE-522 and GeparNuevo. However, the risk of irreversible immune-mediated adverse events (AEs) of the endocrine system due to ICI use supports the use of ICIs only in the cohort of patients at higher risk for disease recurrence. For both the lower and higher risk groups, the study treatments have the potential for the development of de-escalation strategies in this disease setting where traditional chemotherapy regimens may be avoided altogether. While assessment of the efficacy of the combination of olaparib and durvalumab is ongoing, there are sufficient safety data available to develop a safety and tolerability profile for the combination.