LUCY: A phase IIIb, real-world study of olaparib in HER2-negative metastatic breast cancer patients with a BRCA mutation

Background: The Phase III OlympiAD trial (NCT02000622) showed a significant improvement in progression-free survival (PFS) in favour of olaparib vs physician's choice chemotherapy in patients with HER2-negative metastatic breast cancer (mBC) and a germline BRCA mutation (gBRCAm). In January 2018, the US FDA expanded the approved use of olaparib to treat patients with HER2-negative mBC and a gBRCAm. LUCY (NCT03286842) has been initiated to evaluate the clinical effectiveness of olaparib in these patients in a real-world setting, and has been expanded to include a cohort of patients with somatic BRCA mutations (sBRCAm). Trial design: LUCY is an open-label, single-arm, multicentre, international Phase IIIb trial. Patients with HER2-negative mBC and a deleterious BRCAm (gBRCAm or sBRCAm), who have received treatment with taxane or anthracycline in either the adjuvant or metastatic setting, and ≤2 prior lines of chemotherapy for metastatic disease, will be enrolled. Patients will be treated with open-label olaparib tablets (300 mg twice daily) until disease progression, unacceptable toxicity, or other discontinuation criteria. For gBRCAm patients (Cohort 1), the primary objective is to evaluate the clinical effectiveness of olaparib via investigator-assessed PFS (radiological, symptomatic, or clear progression of non-measurable disease); secondary objectives include overall survival, time to second progression, and clinical response rate. These primary and secondary objectives will be exploratory in sBRCAm patients (Cohort 2), and PFS will be assessed by RECIST 1.1. An additional key exploratory objective will be 24-week disease control rate in the subset of all patients with adequately treated, stable brain metastases at baseline. Safety and tolerability will be described. Initial screening across ∼170 sites in 16 countries will be conducted to identify a target sample of 250 patients with gBRCAm and 20 patients with sBRCAm. The first subject was enrolled in Q1 2018. Clinical trial identification: NCT03286842. Editorial acknowledgement: Stephen Paterson, Mudskipper Business Ltd. Legal entity responsible for the study: AstraZeneca. Funding: AstraZeneca. Disclosure: K.A. Gelmon: Consulting or advisory role: AstraZeneca, Eli Lilly, Merck, and Pfizer; Expert opinion: Genentech. G.P. Walker: Contracted services and stockholder; AstraZeneca. G.V. Fisher, S.C. McCutcheon: Employee and stockholder; AstraZeneca.