240MO - Prognostic and predictive impact of estrogen/progesterone receptor (ER/PR), and Ki-67 expression: An exploratory analysis from the monarchE trial in patients with high-risk, HR+, HER2-, early breast cancer (EBC)

Background

The monarchE trial demonstrated that the addition of abemaciclib to endocrine therapy (ET) significantly improved invasive disease-free survival (IDFS) and distant relapse-free survival in node-positive, high-risk EBC patients (pts) with benefit deepening beyond the 2-year (yr) treatment (tx) period. Ki-67 ≥20% was prognostic of breast cancer outcomes but not predictive of abemaciclib benefit. Here, we evaluate expression of ER, PR and Ki-67 to determine their prognostic and predictive impact, including analyses as continuous variables.

Methods

ER/PR and Ki-67 expression was determined by immunohistochemistry (IHC). The graphical Subpopulation (subp) Tx Effect Pattern Plot (STEPP) analysis was conducted for each biomarker to robustly assess the tx effect ensuring a balance between subp sample size and enough number of overlapping subp. Cox proportional hazards model was used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for ER/PR status subtypes (positive ≥1%).

Results

Each IHC cohort varied slightly in number of pts and the precise IDFS HR point estimate (abemacilib+ET vs ET), but STEPP analysis revealed consistent abemaciclib tx benefit regardless of ER, PR or Ki-67 expression (Table, A). The IDFS benefit of abemaciclib was also consistent in ER+/PR+ and ER+/PR- tumors (Table, B). The 3-yr IDFS rates of the control arm showed that pts with PR- tumors had a higher risk of recurrence. Pts with ER- tumors followed a similar trend, but the effect could not be robustly estimated due to small numbers. Table: 240MO

Summary of STEPP and IDFS analysis

IQR, Interquartile range. *Not estimated (NE) due to low numbers

Conclusions

Consistent IDFS benefit of adjuvant abemaciclib was observed regardless of the level of ER, PR or Ki-67 expression, as well as in ER+/PR+ and ER+/PR- tumors. Similar to Ki-67 ≥20%, PR- status was prognostic of worse outcomes with ET alone.

Clinical trial identification

NCT03155997.

Editorial acknowledgement

Monique Mendonca, employee of Eli Lilly and Company, provided medical writing support and editorial assistance.

Legal entity responsible for the study

Eli Lilly and Company.

Funding

Eli Lilly and Company.

Disclosure

M.P. Goetz: Financial Interests, Institutional, Advisory Board: ARC Therapeutics, Biotheranostics, Blueprint Medicines, Rna Diagnostics, Sanofi Genzyme; Financial Interests, Institutional, Other, Consulting: AstraZeneca, Seattle Genetics; Financial Interests, Institutional, Other, General Consulting: Lilly; Financial Interests, Personal, Invited Speaker, CME Activity: Research to Practice, Clinical Education Alliance, Medscape, MJH Life Sciences; Financial Interests, Personal, Invited Speaker, CME Panel Discussant: Total Health Conferencing; Financial Interests, Personal, Other, Moderator for CME Activity: Curio Science; Financial Interests, Institutional, Local PI: Lilly, Pfizer, LOXO, ATOSSA Therapeutics, AstraZeneca, Sermonix. N. Turner: Financial Interests, Personal, Advisory Board: AstraZeneca, Lilly, Novartis, Pfizer, Roche/Genentech, GSK, Zentalis pharmaceuticals, Repare therapeutics, GSK, Relay therapeutics, Gilead, Inivata, Guardant, Exact Sciences; Financial Interests, Institutional, Funding: AstraZeneca, Pfizer, Roche/Genentech, Merck Sharpe and Dohme, Invitae, Inivata, Personalis, Natera; Financial Interests, Institutional, Other, provision of materials: BioRad; Financial Interests, Institutional, Other, Provision of assays: Guardant Health. H. Sasano: Financial Interests, Personal, Full or part-time Employment: Tohoku University . C. Arteaga: Financial Interests, Personal, Speaker, Consultant, Advisor: Novartis, Eli Lilly, Merck, AstraZeneca, Daiichi Sankyo, TAIHO Oncology, PUMA Biotechnology, Immunomedics, OrigiMed, Sanofi; Financial Interests, Personal, Research Funding: Pfizer, Pfizer, Takeda. S. Chandarlapaty: Financial Interests, Personal, Advisory Board, Consultant: Novartis, Boxer Capital, Totus Medicines, Nuvalent, Inivata, Neogenomics; Financial Interests, Institutional, Research Grant: Daiichi Sankyo; Financial Interests, Personal and Institutional, Advisory Board, Consultant: AstraZeneca; Financial Interests, Personal, Research Grant: AstraZeneca; Financial Interests, Personal, Officer: Odyssey Biosciences; Financial Interests, Personal, Stocks/Shares: Odyssey Biosciences. S. Loi: Financial Interests, Institutional, Advisory Board, Consultant: Aduro Biotech, Novartis, GSK, Roche Genentech, AstraZeneca, Silverback Therapeutics, G1 Therapeutics, Pfizer, Seattle Genetics; Financial Interests, Institutional, Advisory Board, COnsultant: PUMA Biotechnologies, BMS; Financial Interests, Institutional, Advisory Board, consultant: Gilead Therapeutics, Daiichi Sankyo, Merck, Amunix, Tallac Therapeutics, Eli Lilly; Financial Interests, Institutional, Funding, Research: Novartis, BMS, Merck, PUMA Biotechnology, Eli Lilly, Roche - Genentech, Nektar Therapeutics, AstraZeneca, Seattle Genetics; Non-Financial Interests, Advisory Role, Consultant (Non remunerated): Seattle Genetics, Novartis, Bristol Myers Squibb, Merck, AstraZeneca, Roche Genentech; Non-Financial Interests, Advisory Role, consultant (not compensated): Pfizer, Eli Lilly, Gilead Therapeutics. J.S. Reis-Filho: Financial Interests, Personal, Other, Consultant: Goldman Sachs, Eli Lilly, Saga Diagnostics; Financial Interests, Personal, Other, Member of the Scientific Advisory Board and Consultant: Repare Therapeutics, Paige.AI; Financial Interests, Personal, Advisory Board: Personalis, Roche Tissue Diagnostics; Financial Interests, Personal, Advisory Board, Member of the Scientific Advisory Board: Bain Capital; Financial Interests, Personal, Advisory Board, Ad hoc member of the Pathology Scientific Advisory Board: Daiichi Sankyo, Merck; Financial Interests, Personal, Advisory Board, Ad hoc member of the Oncology Scientific Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board, Member of the SAB: MultiplexDX; Financial Interests, Personal, Member of Board of Directors: Odyssey Bio, Grupo Oncoclinicas; Financial Interests, Personal, Stocks/Shares: Repare Therapeutics; Financial Interests, Personal, Other, Stock options: Paige.AI. H. Kreipe: Financial Interests, Personal, Other, Payment or honoraria for lectures: Roche Pharma, Novartis, Genomic Health, AstraZeneca, Eli Lilly, Pfizer, Daiichi Sankyo; Financial Interests, Personal, Advisory Board: Roche Pharma, Genomic Health, AstraZeneca. N. Harbeck: Financial Interests, Personal, Speaker’s Bureau, Fees for Non-CME Services Received Directly from Commercial Interest or their Agents: Amgen, AstraZeneca, Daiichi Sankyo, Eli Lilly, Exact Sciences, MSD, Novartis, Pfizer, Pierre Fabre, Seagen; Financial Interests, Personal, Advisory Board, Consulting Fees: AstraZeneca, Daiichi Sankyo, Eli Lilly, MSD, Novartis, Pfizer, Pierre Fabre, Roche, Sandoz, Seagen; Financial Interests, Personal, Sponsor/Funding, Fees for Non-CME Services Received Directly from Commercial Interest or their Agents: Roche; Financial Interests, Personal, Research Funding, Contracted Research: Roche; Financial Interests, Personal, Writing Engagement, Third-party writing assistance for this abstract, furnished by Sunaina Indermun, BPharm, PhD, of Health Interactions: Roche; Financial Interests, Personal, Stocks or ownership: WSG. P. 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, Local PI: BionTech, Cepheid; Non-Financial Interests, Member: ASCO, Arbeitsgemeinschaft für Gynäkologische Onkologie e.V., Translational Research in Oncology, Deutsche Gesellschaft für Senologie e.v. C.S. Rubenstein: Financial Interests, Institutional, Full or part-time Employment: Loxo at Lilly. S. Wijayawardana: Financial Interests, Personal, Full or part-time Employment: Eli Lilly and Company; Financial Interests, Personal, Stocks/Shares: Eli Lilly and Company. M. Muñoz: Financial Interests, Personal, Full or part-time Employment: Eli Lilly and Company; Financial Interests, Personal, Stocks/Shares: Eli Lilly and Company. L.M. Litchfield: Financial Interests, Personal, Full or part-time Employment: Eli Lilly and Company; Financial Interests, Personal, Stocks/Shares: Eli Lilly and Company. S.R.D. Johnston: Financial Interests, Personal, Advisory Board, Consulting Fees: AstraZeneca, Eli Lilly and Company, Pfizer, Biotechnology, Novartis, Sanofi Genzyme, Puma Biotechnology; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, Pfizer, Eisai, Roche/Genentech.