Abstract 63P
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
| Premenopausal | Postmenopausal | |||
| Abemaciclib + ET N=1227 | ET Alone N=1224 | Abemaciclib + ET N=1576 | ET alone N=1605 | |
| IDFS | ||||
| Events, n (%) | 84 (6.8) | 139 (11.4) | 147 (9.3) | 194 (12.1) |
| HR (95% CI) | 0.573 (0.437, 0.751) | 0.798 (0.644, 0.990) | ||
| 2-year rate, % (95% CI) | 94.5 (93.0, 95.7) | 90.4 (88.5, 91.9) | 91.2 (89.7, 92.6) | 89.7 (88.1, 91.2) |
| 3-year rate, % (95% CI) | 89.5 (86.4, 91.9) | 83.8 (80.6, 86.6) | 88.2 (85.9, 90.1) | 83.1 (80.1, 85.6) |
| DRFS | ||||
| Events, n (%) | 72 (5.9) | 116 (9.5) | 118 (7.5) | 162 (10.1) |
| HR (95% CI) | 0.592 (0.441, 0.795) | 0.761 (0.600, 0.966) | ||
| 2-year rate, % (95% CI) | 95.4 (94.0, 96.5) | 92.0 (90.2, 93.4) | 93.2 (91.8, 94.4) | 91.3 (89.8, 92.6) |
| 3-year rate, % (95% CI) | 90.5 (87.4, 92.9) | 86.1 (82.9, 88.7) | 90.1 (88.0, 91.9) | 86.1 (83.5, 88.3) |
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.