Background

In the OlympiAD phase III trial, olaparib significantly prolonged progression-free survival (PFS) vs chemotherapy in patients (pts) with germline-BRCA-mutated (gBRCAm), HER2-negative mBC regardless of hormone receptor (HR) status. In a study population that reflects clinical practice, the phase IIIb LUCY trial similarly showed clinical effectiveness of olaparib regardless of HR status. ASCO/CAP guidelines highlight the lack of data on the best treatment approach for breast tumors that are estrogen receptor (ER)-low (1–10% ER+ stained cells). We examined olaparib clinical effectiveness by ER expression in pts with HER2-negative gBRCAm mBC from the LUCY trial.

Methods

In this open-label trial, pts with germline or somatic BRCAm, HER2-negative mBC received olaparib (300 mg BID). Pts had received ≤2 chemotherapy lines for mBC and a taxane and/or anthracycline in the (neo)adjuvant or mBC setting. Pts with ER+ BC had received endocrine therapy. In this post hoc subgroup analysis (data cut-off Sept 1, 2021), pts with gBRCAm were grouped by ER expression (ER <1%; 1–10%; >10% by IHC) and analysed for PFS, overall survival, clinical response rate (CRR; i.e. the proportion of pts assessed as responding by the investigator [radiological or symptomatic] at ≥1 visit), and duration of clinical response.

Results

251/252 pts in the gBRCAm cohort were included (ER <1% n=117; 1–10% n=29; >10% n=105). At baseline, pts in the ER <1% group had shorter median times from their original diagnosis (29.7 vs 52.0 vs 58.6 mo) and from diagnosis of mBC (4.8 vs 11.1 vs 12.5 mo) vs pts in the ER 1–10% and >10% groups, respectively. Efficacy outcomes with olaparib were consistent across ER expression subgroups (Table). Table: 203P

Efficacy results by ER expression

Conclusions

Real-world results of the phase IIIb LUCY trial support the clinical effectiveness of olaparib in pts with gBRCAm, HER2-negative mBC, regardless of ER expression level.

Clinical trial identification

NCT03286842.

Editorial acknowledgement

Writing and editorial assistance was provided by Leigh-Ann Booth, PhD of BOLDSCIENCE Inc., funded by AstraZeneca and MSD.

Legal entity responsible for the study

AstraZeneca.

Funding

This study was supported by AstraZeneca and Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, who are codeveloping olaparib (MSD).

Disclosure

K.A. Gelmon: Financial Interests, Personal, Advisory Board: AstraZeneca, Ayala, Gilead, Lilly, Merck, Novartis, Pfizer, Seagen; Non-Financial Interests, Institutional, Principal Investigator: AstraZeneca, BMS, Pfizer. P.A. Fasching: Financial Interests, Personal, Advisory Board: Roche, Novartis, Pfizer, Daiichi Sankyo, Eisai, Merck, Sharp & Dohme, AstraZeneca, Hexal, Lilly, Pierre Fabre, Seagen, Agendia, Sanofi Aventis; Financial Interests, Personal, Invited Speaker: Novartis, Daiichi Sankyo, Eisai, Merck, Sharp & Dohme, AstraZeneca, Lilly, Seagen, Gilead; Financial Interests, Personal, Other, Medical Writing Support: Roche; Financial Interests, Institutional, Invited Speaker: BionTech, Cepheid; Non-Financial Interests, Member: ASCO, Arbeitsgemeinschaft für Gynäkologische Onkologie e.V., Translational Research in Oncology, Deutsche Gesellschaft für Senologie e.v. S. Delaloge: Financial Interests, Institutional, Advisory Board: AstraZeneca, Novartis, Pierre Fabre, Orion, Sanofi, Rappta, Cellectis, Isis/servier; Financial Interests, Institutional, Invited Speaker: Exact Sciences, Pfizer, Seagen, Lilly, AstraZeneca, MSD, Roche Genentech, BMS, Puma, AstraZeneca, Orion, Sanofi, Pfizer; Financial Interests, Institutional, Advisory Board, ad board: Besins Healthcare; Financial Interests, Institutional, Invited Speaker, ESMO symposium: Gilead; Financial Interests, Institutional, Advisory Board, scientific board: Elsan; Financial Interests, Institutional, Funding: GE; Financial Interests, Institutional, Invited Speaker, clinical research funding to my institution: Taiho; Non-Financial Interests, Invited Speaker, Société Française de Sénologie et Pathologie Mammaire: SFSPM; Non-Financial Interests, Principal Investigator, H2020 funding: European Commission. Y.H. Park: Financial Interests, Personal and Institutional, Writing Engagements, Financial and non-financial relationships are declared: Novartis, Pfizer, Merck, Roche, Lilly, AstraZeneca, Daiichi Sankyo; Financial Interests, Personal and Institutional, Advisory Board, Financial and non-financial relationships are declared: Novartis, Pfizer, Merck, Roche, Lilly, AstraZeneca, Eisai, Daiichi Sankyo, Menarini, Gilead Sciences, Boryung; Financial Interests, Personal and Institutional, Principal Investigator, Financial and non-financial relationships are declared: Novartis, Pfizer, Merck, Roche, Lilly, AstraZeneca, Daiichi Sankyo, Menarini, Gilead Sciences, Boryung, Gencurix; Financial Interests, Personal and Institutional, Invited Speaker, Financial and non-financial relationships are declared: Pfizer, Merck, Roche, Lilly, AstraZeneca, Eisai, Daiichi Sankyo; Financial Interests, Personal and Institutional, Research Grant, Financial and non-financial relationships are declared: Pfizer, Merck, Roche, Lilly, AstraZeneca, Gencurix, Genome Insight, NGenbio. A.F. Eisen: Financial Interests, Institutional, Invited Speaker, Local PI for Brevity Study: RNA Diagnostics; Financial Interests, Institutional, Invited Speaker, Local PI for LUCY study: Astra-Zeneca. Z. Kemp: Financial Interests, Personal, Invited Speaker: AstraZeneca, Lilly; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Principal Investigator: AstraZeneca. J. Sohn: Financial Interests, Personal, Stocks/Shares, Immediate Family Member: Daiichi Sankyo; Financial Interests, Institutional, Research Grant: MSD, Roche, Novartis, AstraZeneca, Lilly, Pfizer, GSK, Daiichi Sankyo, Sanofi, Boehringer Ingelheim, Seagen. C.V. Timcheva: Financial Interests, Personal, Advisory Board, Guidelines for the treatment o TNBC: Gilead; Financial Interests, Personal, Other, PI of clinical trial: AstraZeneca; Financial Interests, Personal and Institutional, Invited Speaker, PI for several clinical trials performing in the hospital: AstraZeneca, Parexel; Financial Interests, Personal and Institutional, Invited Speaker, Pi for several clinical trials perforing in the hospital: Roche; Financial Interests, Personal and Institutional, Invited Speaker, PI for some clinical trials performing in the hospital: Novartis; Financial Interests, Personal and Institutional, Invited Speaker, PI for the clinical trial performing in the hospital: I3Research; Non-Financial Interests, Principal Investigator, Investigator initiated trial on metastatic CRC: Merck. T. Park-Simon: Financial Interests, Personal and Institutional, Invited Speaker: Roche, GSK, AstraZeneca, Pfizer, Lilly, Daiichi Sankyo, Seagen, Gilead, Eisai, MSD; Financial Interests, Personal and Institutional, Advisory Board: Roche, GSK, AstraZeneca, Pfizer, Lilly, Daiichi Sankyo, Seagen, Gilead, Eisai, MSD; Financial Interests, Personal and Institutional, Principal Investigator: Roche, GSK, AstraZeneca, Pfizer, Lilly, Daiichi Sankyo, Seagen, Gilead, Eisai, MSD. A. Anton Torres: Financial Interests, Personal, Invited Speaker: AstraZeneca-Daiichi Sankyo, Eli Lilly, Seagen; Financial Interests, Personal, Advisory Board: AstraZeneca-Daiichi Sankyo, Eli Lilly, Gilead; Financial Interests, Personal, Expert Testimony: Pfizer, Eli Lilly. E. John, N. Lukashchuk, K. Baria: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. I. Gibson: Financial Interests, Personal, Full or part-time Employment: AstraZeneca. J. Balmaña: Financial Interests, Personal, Advisory Board: AstraZeneca, Pfizer; Financial Interests, Institutional, Invited Speaker: Pfizer, AstraZeneca, MedSir. All other authors have declared no conflicts of interest.