Abstract OT3-04-04: LUCY: A phase IIIb, single-arm, open-label multicenter study of olaparib in patients with HER2-negative metastatic breast cancer and a germline <i>BRCA1/2</i> mutation
Authors: K Gelmon, GP Walker, GV Fisher
Journal: Cancer Research (2018)

Abstract Background Olaparib (Lynparza) is a PARP inhibitor with activity in patients with advanced cancers who have a germline BRCA1 and/or BRCA2 (gBRCA) mutation and is licensed for use in gBRCA-mutated recurrent ovarian cancer. The Phase III OlympiAD trial (NCT02000622) in HER2-negative metastatic breast cancer (mBC) patients with a gBRCA mutation showed a significant progression-free survival (PFS) improvement in favor of olaparib compared with physician's choice of chemotherapy treatment (hazard ratio [HR] 0.58; 95% confidence interval [CI] 0.43–0.80; P&amp;lt;0.001; 7.0 vs 4.2 months, respectively) (Robson et al. NEJM 2017). The LUCY trial (EudraCT number: 2017-001054-34) has been initiated to further evaluate the clinical effectiveness of olaparib in a real-world setting, and to help inform and guide clinical practice. Trial design LUCY is an open-label, single-arm, multicenter, international Phase IIIb trial. All patients will be treated with open-label olaparib tablets (300 mg twice daily) until disease progression, unacceptable toxicity, or other discontinuation criteria. Eligibility criteria Eligible patients aged ≥18 years will have a gBRCA mutation and HER2-negative mBC. Patients are required to have received a prior taxane or anthracycline in either the adjuvant or metastatic setting, but should not have received &amp;gt;1 line of chemotherapy in the metastatic setting. Hormone receptor-positive patients are also required to have received and progressed with ≥1 prior endocrine therapy. Patients will be required to have an expected survival of &amp;gt;6 months. Objectives The primary objective is to evaluate the clinical effectiveness of olaparib through investigator-defined assessment of PFS (radiological, symptomatic, or clear progression of non-measurable disease). Secondary objectives will include assessments of overall survival (OS), time to first/second subsequent therapy, time to second progression and time to study treatment discontinuation, as well as assessment of clinical response rate and duration of clinical response. Safety and tolerability will also be described. Statistical methods Approximately 2500 patients will be screened to identify 250 patients with a gBRCA mutation. The primary analysis of PFS will be performed after 160 progression events: assuming a median PFS of 7 months, the predicted 95% CI for the median is 6.0–8.2 months. Analysis of OS and updated PFS will be performed after 160 deaths: assuming a median OS of 19 months, the predicted 95% CI for the median is 16.3–22.2 months. PFS and OS will be summarized using a Kaplan–Meier plot, from which the median and 95% CI data will be calculated. Present accrual Screening is expected to take place across ˜180 sites in 17 countries. Summary LUCY will provide further data on the efficacy of olaparib in the real-world setting of mBC in patients with gBRCA mutation. Citation Format: Gelmon K, Walker GP, Fisher GV. LUCY: A phase IIIb, single-arm, open-label multicenter study of olaparib in patients with HER2-negative metastatic breast cancer and a germline BRCA1/2 mutation [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr OT3-04-04.