274P - Impact of dose reductions on efficacy of adjuvant abemaciclib for patients with high-risk early breast cancer (EBC): Analyses from the monarchE study

Background

Abemaciclib is approved as adjuvant therapy for HR+, HER2-, high risk EBC based on clinically significant improvements in invasive disease-free survival (IDFS) and distant relapse-free survival (DRFS), which were maintained and deepened after the 2-year treatment period was completed. In monarchE, 44% of patients required dose reductions of abemaciclib to proactively manage adverse events. In abemaciclib MBC trials, similar rates of dose reductions did not compromise PFS (Rugo, 2021). Here we present the exploratory analyses to investigate the impact of dose reductions on efficacy in monarchE.

Methods

In monarchE, up to 2 abemaciclib dose reductions were permitted prior to discontinuation. Pts treated with abemaciclib were classified into 3 equal-sized subgroups according to their abemaciclib relative dose intensity (RDI), and IDFS rates were estimated within each subgroup. A time-dependent Cox proportional hazard (PH) model ( Therneau, 2000 ) was also implemented to assess the impact of dose levels over time on IDFS.

Results

Among the 2791 pts treated with abemaciclib, 832 (30%) had one and 389 (14%) had two dose reductions. Patients ≥65 years old, or those with ≥4 pre-existing co-morbidities were more likely to have dose reductions. Across the 3 RDI groups (≤66% vs 66%-93% vs ≥93%), 4-year IDFS rates were generally consistent (87.1% vs 86.4% vs 83.7% from the lowest RDI group to the highest). According to the time-dependent model, the effect of abemaciclib is similar when staying at the full 150mg dose compared to being dose reduced to either 100mg or 50mg (HR = 0.905; 95% CI = 0.727, 1.125).

Conclusions

Consistent with observations in the metastatic setting, the efficacy of adjuvant abemaciclib in monarchE was not compromised by dose reductions. Therefore, dose reductions should be considered as a safe and effective way to manage toxicity and retain patients on treatment, in order to maintain benefit from adjuvant abemaciclib in combination with endocrine therapy.

Clinical trial identification

NCT03155997.

Editorial acknowledgement

Trish Huynh, employee of Eli Lilly and Company, provided medical writing support.

Legal entity responsible for the study

Eli Lilly and Company.

Funding

Eli Lilly and Company.

Disclosure

J. O'Shaughnessy: Financial Interests, Other, Consulting, payment or honoraria for lectures, presentations, speaker's bureaus, manuscript writing, or educational events: AbbVie, Agendia, Amgen, Aptitude, AstraZeneca, Athenex, Bayer, Bristol Myers Squibb, Carrick Therapeutics , Celgene, Daiichi Sankyo, Eisai, Genzyme, Gilead, Heron, Immunomedics, Lilly, Seagen, Syndax; Financial Interests, Other, Consulting, payment or honoraria for lectures, presentations, speaker's bureaus, manuscript writing, or educational events fees: G1 therapeutics, Genentech, Grail, Halozyme, Ipsen, Merck, Myriad, Nektar, Novartis, Ontada, Pfizer, Pharmacyclics, Pierre Fabre, Puma, Prime Oncology, Roche, Samsung BIoepis, Sandoz, Sanofi, Taiho, Takeda, Theralink, Synthon. I. Cicin: Other, Principal investigator for Jounce Therapeutic: Jounce Therapeutic. L. Testa: Financial Interests, Local PI, All support for the present manuscript (e.g., funding, provision of study materials, medical writing, article processing charges, etc.) No time limit for this item. Lilly As the trial sponsor, Lilly funded the study and payed for all processing charges: Eli Lilly and Company; Financial Interests, Institutional, Research Funding, 2 Grants or contracts from any entity (if not indicated in item #1 above). Novartis Grant for clinical research at other institution: Novartis; Financial Interests, Advisory Board: MSD, Eli Lilly and Company, AstraZeneca, Novartis, Daiichi Sanko; Financial Interests, Other, Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: MSD, Eli Lilly an Company, Pfizer, Daiichi Sankyo, Novartis, AstraZeneca; Financial Interests, Other, Support for attending meetings and/or travel: Pfizer, AstraZeneca, Gilead; Financial Interests, Other, Leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid: AstraZeneca. S.M. Tolaney: Financial Interests, Personal, Advisory Board, Ad board participant/consultant: 4D Pharma, ARC Therapeutics, Daiichi Sankyo, Eisai, Genentech/Roche, Gilead, Novartis, Sanofi, SeaGen; Financial Interests, Personal, Other, Consulting: Aadi BioPharma; Financial Interests, Personal, Advisory Board, Ad board participation: Artios, Incyte Corp, BeyondSprings; Financial Interests, Personal, Advisory Board, Ad Board Participant/Consultant: AstraZeneca, Eli Lilly; Financial Interests, Personal, Advisory Board, Advisory Board participation: Bayer, Infinity Therapeutics, Myovant, OncXerna, Umoja Biopharma, Zentalis, Zetagen; Financial Interests, Personal, Other, Consultant: Blueprint Medicines; Financial Interests, Personal, Advisory Board, Ad board participant: Bristol Myers Squibb, Ellipses Pharma, Mersana Therapeutics; Financial Interests, Personal, Other, Steering Committee Member/Consultant: CytomX; Financial Interests, Personal, Advisory Board, Advisory Board participation/consulting: Menarini/Stemline; Financial Interests, Personal, Advisory Board, Ad Board participant/consultant: Merck; Financial Interests, Personal, Advisory Board, Ad board participant/Consultant: Pfizer; Financial Interests, Personal, Advisory Board, Advisory board participation: Reveal Genomics; Financial Interests, Personal, Advisory Board, Advisory Board Participation: Zymeworks; Financial Interests, Institutional, Funding: AstraZeneca, Eli Lilly, Pfizer, Sanofi, SeaGen, Odonate, Cyclacel, Exelixis, Gilead, Bristol Myers Squibb, Eisai, Merck, Novartis, Nektar, Genentech/Roche; Financial Interests, Personal and Institutional, Steering Committee Member: CytomX. J. Huober: Financial Interests, Institutional, Other, Grants or contracts from any entity: Celgene, Novartis, Hexal, Eli Lilly and Company; Financial Interests, Personal, Other, Consulting fees: Eli Lilly and Company, Novartis, Roche, Pfizer, Novartis , Celgene, Daiichi, Gilead; Financial Interests, Personal, Other, Payment or honoraria for lectures presentations speaker's bureau manuscript writing or educational events: Eli Lilly and Company, Novartis, Roche, Pfizer, AstraZeneca, MSD, Celgene , Eisai, AbbVie, Seagen, Gilead; Financial Interests, Personal, Other, Support for attending meetings and travel: Roche, Pfizer, Novartis, Celgene, Daiichi , Gilead . V. Guarneri: Financial Interests, Personal, Invited Speaker: Eli Lilly, Novartis, Amgen, GSK; Financial Interests, Personal, Advisory Board: Eli Lilly, Novartis, MSD, Gilead, Eli Lilly, Sanofi, Merck Serono, Exact Sciences, Eisai, Olema Oncology; Financial Interests, Institutional, Local PI: Eli Lilly, Roche, BMS, Novartis, AstraZeneca, MSD, Synton Biopharmaceuticals, Merck, GSK, Daiichi Sankyo, Nerviano; Non-Financial Interests, Member: ASCO. S.R.D. Johnston: Financial Interests, Personal and Institutional, Advisory Role, Research funding to institue for clinical trials: Eli Lilly and Company, AstraZeneca, Pfizer, Novartis; Financial Interests, Personal and Institutional, Advisory Role, Research funding to institute for laboratory studies: Biotechnology, Puma Biotechnology ; Financial Interests, Personal, Advisory Role: Sanofi Genzyme; Financial Interests, Personal, Speaker’s Bureau: Eisai; Financial Interests, Personal and Institutional, Speaker’s Bureau, Research funding to institute for clinical trials: Roche/Genentech. M. Martin Jimenez: Financial Interests, Personal, Advisory Board: AstraZeneca, Lilly, Roche/Genentech, Daiichi Sankyo, Menarini-Stemline; Financial Interests, Personal, Invited Speaker: Pfizer, AstraZeneca, Lilly, Novartis, Roche/Genentech; Financial Interests, Institutional, Research Grant: Novartis, Roche, Puma; Non-Financial Interests, Member of Board of Directors: TRIO; Non-Financial Interests, Leadership Role: GEICAM; Non-Financial Interests, Member: ASCO; Non-Financial Interests, Advisory Board: SEOM. N. Harbeck: Financial Interests, Other, Consulting fees: Gilead, Sandoz, Seagen; Financial Interests, Other, Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: Amgen, AstraZeneca, Daiichi Sankyo, Gilead, Lilly, MSD, Novartis, Pierre Fabre, Pfizer, Roche, Seagen; Financial Interests, Other, Participation on a Data Safety Monitoring Board or Advisory Board: Roche; Other, Leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid: West German Study Group, ESMO. H.S. Rugo: Financial Interests, Personal, Other, Consultancy/advisory support: PUMA, NAPO, Mylan, Daiichi Sankyo, Eisai; Financial Interests, Institutional, Local PI: Novartis, Lilly, Pfizer, Daiichi, AstraZeneca, Gilead Sciences, Inc., GSK, Sermonix Pharmaceuticals Ins., Pionyr Immunotherapeutics, Taiho Oncology, Inc., Veru Inc; Financial Interests, Institutional, Coordinating PI: OBI Pharma, Astellas Pharma Inc., F. Hoffmann-La Roche AG/Genentech, Inc., Merck; Financial Interests, Personal, Other, Travel support to academic meetings: Merck, AstraZeneca, Gilead; Non-Financial Interests, Advisory Role, I advise a number of companies without compensation: various. R.J. Wei: Financial Interests, Personal, Stocks/Shares: Eli Lilly and Company; Financial Interests, Personal, Full or part-time Employment: Eli Lilly and Company. V. Andre: Financial Interests, Personal, Full or part-time Employment: Eli Lilly and Company; Financial Interests, Personal, Stocks/Shares: Eli Lilly and Company. A. Shahir: Financial Interests, Personal, Stocks or ownership: Eli Lilly and Company; Financial Interests, Personal, Full or part-time Employment: Eli Lilly and Company. 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. All other authors have declared no conflicts of interest.