Background

Abemaciclib is the first and only approved CDK4 & 6 inhibitor in the adjuvant setting for certain types of HR+, HER2-, node-positive, high-risk early breast cancer (EBC). Patient (Pts) with HR+, HER2- tumors who are premenopausal (preM) may have a different tumor biology and response to endocrine therapy (ET) than postmenopausal (postM) pts, warranting analysis of the prespecified subgroup within monarchE.

Methods

Randomized (1:1) pts received adjuvant ET +/- abemaciclib for 2 years (yrs) plus at least 3 yrs of ET as clinically indicated. Menopausal status (preM vs. postM) at diagnosis was a predefined stratification factor. Standard ET (tamoxifen or an aromatase inhibitor), with or without additional GnRH, was determined by physician’s choice. Baseline disease characteristics and ET choice were described at ESMO, 2021. Efficacy and safety results of abemaciclib + ET vs. ET alone including invasive disease-free survival (IDFS) and distant relapse-free survival (DRFS) were assessed by menopausal status with a data cut-off date on 1 April 2021, at a median follow-up of 27 months.

Results

Among randomized pts, 2451 (43.5%) were preM and 3181 (56.4%) postM. Treatment benefit was consistent in both menopausal status subgroups, with numerically greater effect size in preM subgroup compared to postM subgroup (Table). For preM pts, abemaciclib + ET resulted in a 42.7% and 40.8% reduction in risk of developing an IDFS and DRFS event, respectively. The absolute improvement at 3 yrs was 5.7% for IDFS and 4.4% for DRFS rates. The safety profile for preM pts was consistent with the safety population. Table: 63P

Efficacy data by menopausal status

Conclusions

Abemaciclib + ET demonstrated a clinically meaningful treatment benefit in IDFS and DRFS vs. ET alone regardless of menopausal status, with a numerically greater benefit in the preM population. Safety data in preM pts is consistent with the overall safety profile of abemaciclib.

Clinical trial identification

NCT03155997.

Editorial acknowledgement

Medical writing support was provided by Trish Huynh (Eli Lilly and Company, IN, USA).

Legal entity responsible for the study

Eli Lilly and Company.

Funding

Eli Lilly and Company.

Disclosure

S. Paluch-Shimon: Financial Interests, Institutional, Advisory Board, Advisory board invited speaker honoraria: Roche; Financial Interests, Institutional, Other, Advisory board invited speaker honoraria: Pfizer; Financial Interests, Institutional, Other, Advisory board invited speaker honoraria: Novartis; Financial Interests, Institutional, Other, Advisory board invited speaker honoraria: AstraZeneca; Financial Interests, Institutional, Advisory Board, Advisory board invited speaker honoraria: Exact sciences; Financial Interests, Institutional, Advisory Board, Advisory board invited speaker honoraria: Eli Lilly; Financial Interests, Institutional, Other, Advisory board, speaker's bureau, consultancy: Medison; Financial Interests, Personal and Institutional, Research Grant, Research grant for an RFP independent research put out by SPCC and Pfizer: SPCC (Shared Progress in Cancer Care). P. Neven: Financial Interests, Institutional, Advisory Board: Eli Lilly; Financial Interests, Institutional, Advisory Board: AstraZeneca; Financial Interests, Institutional, Advisory Board: Novartis; Financial Interests, Institutional, Advisory Board: Pfizer; Financial Interests, Institutional, Advisory Board: Roche; Financial Interests, Institutional, Advisory Board: Roularta Belgium; Financial Interests, Personal, Other, Lecture fees: Eli Lilly; Financial Interests, Personal, Other, Lecture fees: Novartis; Financial Interests, Personal, Other, Lecture fees: Pfizer; Financial Interests, Personal, Other, Lecture fees: AstraZeneca. J. Huober: Financial Interests, Research Grant: Celgene; Financial Interests, Research Grant: Novartis; Financial Interests, Research Grant: Hexal; Financial Interests, Research Grant: Eli Lilly and Company; Financial Interests, Other, Honoraria: Eli Lilly and Company; Financial Interests, Other, Honoraria: Novartis; Financial Interests, Other, Honoraria: Roche; Financial Interests, Other, Honoraria: Pfizer; Financial Interests, Other, Honoraria: AstraZeneca; Financial Interests, Other, Honoraria: MSD; Financial Interests, Other, Honoraria: Celgene; Financial Interests, Other, Honoraria: Eisai; Financial Interests, Other, Honoraria: AbbVie; Financial Interests, Other, Honoraria: Seagen; Financial Interests, Other, Honoraria: Gilead; Financial Interests, Advisory Role: Eli Lilly and Company; Financial Interests, Advisory Role: Novartis; Financial Interests, Advisory Role: Roche; Financial Interests, Advisory Role: Pfizer; Financial Interests, Advisory Role: Hexal; Financial Interests, Advisory Role: AstraZeneca; Financial Interests, Advisory Role: MSD; Financial Interests, Advisory Role: Celgene; Financial Interests, Advisory Role: AbbVie; Financial Interests, Advisory Role: Seagen; Financial Interests, Advisory Role: Gilead; Financial Interests, Other, Travel expenses: Roche; Financial Interests, Other, Travel expenses: Pfizer; Financial Interests, Other, Travel expenses: Novartis; Financial Interests, Other, Travel expenses: Celgene; Financial Interests, Other, Travel expenses: Daiichi. Z. Jiang: Financial Interests, Advisory Board: Eli Lilly and Company; Financial Interests, Advisory Board: Roche; Financial Interests, Advisory Board: AbbVie; Financial Interests, Advisory Board: AstraZeneca; Financial Interests, Advisory Board: Pfizer; Financial Interests, Advisory Board: Bayer; Financial Interests, Advisory Board: Novartis; Financial Interests, Advisory Board: Amgen; Financial Interests, Advisory Board: Glaxo Smith Kline; Financial Interests, Advisory Board: Boehringer Ingelheim. M.P. Goetz: Other, Institutional, Other, Consulting: Eagle Pharmaceuticals; Other, Institutional, Other, Consulting: Eli Lilly and Company; Other, Institutional, Other, Consulting: Biovica; Other, Institutional, Other, Consulting: Novartis; Other, Institutional, Other, Consulting: Sermonix; Financial Interests, Institutional, Research Grant: Pfizer; Non-Financial Interests, Institutional, Research Grant: Eli Lilly and Company; Other, Institutional, Other, Consulting: Pfizer; Other, Institutional, Other, Consulting: Biotheranostics; Financial Interests, Institutional, Research Grant: Sermonix; Other, Institutional, Other, Consulting: AstraZeneca; Other, Institutional, Other, Consulting: Blueprint Medicines; Other, Personal, Other, Consulting: Research to Practice; Other, Personal, Other, Consulting: Clinical Education Alliance. C. Shimizu: Financial Interests, Research Grant: Eli Lilly and Company; Financial Interests, Personal, Invited Speaker, Lecture Fee: Daiichi Sankyo; Financial Interests, Personal, Other, Honoraria: Pfizer; Financial Interests, Personal, Invited Speaker, Lecture Fee: Chugai; Financial Interests, Personal, Invited Speaker, Lecture Fee: Taiho; Financial Interests, Personal, Other, Honoraria: AstraZeneca. C. Huang: Financial Interests, Personal, Advisory Board: Eli Lilly and Company; Financial Interests, Personal, Speaker’s Bureau: Amgen; Financial Interests, Personal, Research Grant, Advisory board, Speaker bureau, travel expense: AstraZeneca; Financial Interests, Personal, Advisory Board: EirGenix; Financial Interests, Research Grant: MSD; Financial Interests, Personal, Invited Speaker, Advisory board, speaker bureau: Novartis; Financial Interests, Research Grant: Daiichi Sankyo; Financial Interests, Research Grant: OBI Pharma; Financial Interests, Personal, Research Grant, advisory board, speaker bureau, travel expense: Pfizer; Financial Interests, Personal, Research Grant, advisory board, speaker bureau, travel expense: Roche. R.J. Wei, S.C. Nabinger, T. Forrester: Financial Interests, Personal, Full or part-time Employment: Eli Lilly and Company; Financial Interests, Personal, Stocks/Shares: Eli Lilly and Company. N. Harbeck: Financial Interests, Personal, Other, Lectures, Consulting: Pfizer; Financial Interests, Personal, Other, Lectures, Consulting: AstraZeneca; Financial Interests, Personal, Other, Lectures, Consulting: Eli Lilly and Company; Financial Interests, Personal, Other, Lectures, Consulting: Novartis. All other authors have declared no conflicts of interest.

Background

The emerging treatment paradigm in eBC, with new systemic therapies varying in efficacy, safety and conditions of use, creates a complex patient journey involving many inflection points with respect to treatment sequence, duration and response to initial therapy. We quantified patient preferences for attributes of different treatment pathways in eBC in Germany, Italy and Japan.

Methods

Patients diagnosed with HER2-negative stage I–IIIa breast cancer after 2014 who had undergone surgery and chemotherapy completed an online survey that included a DCE to assess attribute preferences of treatments for eBC. In 12 DCE tasks, patients indicated their preference between 2 hypothetical treatment profiles that varied in 8 attributes. Preference weights for each attribute level and relative attribute importance (RI) were estimated using hierarchical Bayesian modelling and calculated as a percentage based on the difference from the most to least favourable attribute level.

Results

Overall, 452 patients (Germany 151, Italy 151, Japan 150) participated; median (range) age was 48 (19–78) years; 80% were employed and most patients were satisfied (64%) or very satisfied (18%) with the prior therapy they received. Reducing risk of a serious side effect from 77% to 6% was most important (RI=27%), followed by increasing cancer-free survival at 3 years from 67% to 87% (RI=19%), decreasing treatment duration from 18 to 3 months (RI=16%) and reducing risk of nausea from 67% to 2% (RI=14%). Choice of a flexible vs fixed treatment plan was as important as reducing risk of neuropathy from 21% to 1% or fatigue from 41% to 3% (RI=7% for all). Choice of an oral vs intravenous regimen was least important (RI=5%). Some treatment attribute preferences differed by country; notably, efficacy was more important to patients in Japan.

Conclusions

Overall, this international cohort of patients regard the risk of serious side effects, treatment efficacy and treatment duration as highly important. Additionally, these patients would prefer a flexible treatment plan, with treatment escalation/de-escalation in line with response to initial therapy, over a fixed plan. This information may enhance physician–patient interactions in eBC.

Editorial acknowledgement

Editorial assistance was provided by Aaron Borg, PhD of PharmaGenesis Cambridge, Cambridge, UK, with funding from AstraZeneca and Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.

Legal entity responsible for the study

AstraZeneca.

Funding

This study was funded by AstraZeneca and is part of an alliance between AstraZeneca and Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

Disclosure

A. Gennari: Financial Interests, Personal, Invited Speaker: Eisai; Financial Interests, Personal, Advisory Board: Eisai; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Expert Testimony: Gentili; Financial Interests, Personal, Advisory Board: Daiichi Sankyo; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Lilly; Financial Interests, Personal, Invited Speaker: Lilly. C. Jackisch: Financial Interests, Personal, Other, Honoraria, Consultancy, travel and accommodation expenses: AstraZeneca; Financial Interests, Personal, Other, Consultancy, travel and accommodation expenses: Lilly; Financial Interests, Personal, Leadership Role, Travel and accommodation expenses: Novartis; Financial Interests, Personal, Invited Speaker, Consultancy, travel and accommodation expenses: Roche. S. McCutcheon: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. E. Flood: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. B. Murali: Financial Interests, Personal, Full or part-time Employment: Cerner Enviza; Financial Interests, Personal, Other, Provides consultancy services to AstraZeneca as an employee of Cerner Enviza: AstraZeneca. X. Guillaume: Financial Interests, Personal, Full or part-time Employment: Cerner Enviza; Financial Interests, Personal, Other, Provides consultancy services to AstraZeneca as an employee of Cerner Enviza: AstraZeneca. O. Will: Financial Interests, Personal, Full or part-time Employment: Cerner Enviza; Financial Interests, Personal, Other, Provides consultancy services to AstraZeneca as an employee of Cerner Enviza: AstraZeneca. C. Shimizu: Financial Interests, Institutional, Research Grant: Chugai; Financial Interests, Personal, Other, Honoraria: Chugai; Financial Interests, Personal, Other, Honoraria: Eisai; Financial Interests, Personal, Other, Honoraria: Pfizer; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Research Grant: Eli Lilly; Financial Interests, Institutional, Research Grant: Taiho. S. Mokiou: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca.