Endocrine Therapy With or Without Abemaciclib (LY2835219) Following Surgery in Participants With Breast Cancer

• Abemaciclib (Drug), also known as LY2835219: Administered orally.
• Standard Adjuvant Endocrine Therapy (Drug): Administered according to label instructions.

Primary outcomes

• Invasive Disease Free Survival (IDFS) [Baseline to Recurrence or Death from Any Cause (Up to 32 Months)]: IDFS, as defined by the STEEP System, was measured from the date of randomization to the date of first occurrence of one of the following events: ipsilateral invasive breast tumor recurrence, regional invasive breast cancer recurrence, distant recurrence, contralateral invasive breast cancer, second primary non-breast invasive cancer, death attributable to any cause.

Secondary outcomes

• IDFS for Participants With Ki-67 Index ≥20% [Baseline to Recurrence or Death from Any Cause (Approximately 10 Years)]: Outcome data will be provided after the study is completed.
• Distant Relapse-Free Survival (DRFS) [Baseline to Distant Recurrence or Death from Any Cause (Up to 32 Months)]: Distant relapse-free survival is defined as the time from randomization to distant recurrence or death from any cause, whichever occurs first.
• Overall Survival (OS) [Baseline to Death from Any Cause (Approximately 10 Years)]: Outcome data will be provided after the study is completed.
• Pharmacokinetics (PK): Minimum Steady State Concentration (Cmin,ss) of Abemaciclib [Day 1 (2 hours post-dose), Days 30, 60, 90 post-dose]: Pharmacokinetics (PK): Minimum Steady State Concentration (Cmin,ss) of Abemaciclib
• Change From Baseline on the Functional Assessment of Cancer Therapy - Breast (FACT-B) [Baseline, Follow Up (Approximately 3 Years)]: Outcome data will be provided after the study is completed.
• Change From Baseline on the Functional Assessment of Cancer Therapy - Endocrine Symptoms (FACT-ES) [Baseline, Follow Up (Approximately 3 Years)]]: Outcome data will be provided after the study is completed.
• Change From Baseline on the Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) [Baseline, Follow Up (Approximately 3 Years)]]: Outcome data will be provided after the study is completed.
• Change From Baseline on the EuroQol Five-Dimension Five-Level Questionnaire (EQ-5D-5L) [Baseline, Follow Up (Approximately 3 Years)]]: Outcome data will be provided after the study is completed.

Sex: All, ages: 18 Years to any

Inclusion Criteria:

* Women (regardless of menopausal status) or men ≥18 years of age (or per local regulations).
* The participant has confirmed HR+, HER2-, early stage resected invasive breast cancer without evidence of distant metastases.
* The participant must have undergone definitive surgery of the primary breast tumor.
* The participant must have tumor tissue from breast (preferred) or lymph node for exploratory biomarker analysis available prior to randomization.
* Pathologic lymph node involvement and at least one of the following indicating a higher risk of recurrence:

  * 4 or more positive axillary lymph nodes
  * Tumor size of at least 5 centimeters
  * Grade 3 defined as at least 8 points on the Bloom Richardson grading system
  * Ki-67 index by central analysis of ≥20% on untreated breast tissue
* The participant must be randomized within 16 months from the time of definitive breast cancer surgery.
* The participant may receive up to 12 weeks of endocrine therapy until randomization following the last non-endocrine therapy (surgery, chemotherapy, or radiation) whichever is last.
* Participants must have recovered (grade ≤1) from the acute effects of chemotherapy and radiotherapy and from surgical side effects following definitive breast surgery.
* Women of reproductive potential must have a negative blood pregnancy test and agree to use highly effective contraceptive methods.
* The participant has a Eastern Cooperative Oncology Group (ECOG) performance status ≤1.
* The participant has adequate organ function.
* The participant is able to swallow oral medications.

Exclusion Criteria:

* Metastatic disease (including contralateral axillary lymph nodes) or node-negative disease.
* Participants with inflammatory breast cancer.
* Participants with a history of previous breast cancer, with the exception of ipsilateral ductal carcinoma in situ (DCIS) treated by locoregional therapy alone ≥5 years ago. Participants with a history of contralateral DCIS treated by local regional therapy at any time may be eligible. Participants with a history of any other cancer (except non-melanoma skin cancer or carcinoma in situ of the cervix), unless in complete remission with no therapy for a minimum of 5 years from the date of randomization are excluded.
* Females who are pregnant or lactating.
* The participant has previously received treatment with any CDK4 and CDK6 inhibitor.
* The participant is receiving concurrent exogenous reproductive hormone therapy (for example, birth control pills, hormone replacement therapy, or megestrol acetate).
* The participant has previously received endocrine therapy for breast cancer prevention (tamoxifen or aromatase inhibitors) or raloxifene.
* The participant has serious preexisting medical condition(s) that, in the judgment of the investigator, would preclude participation in this study.
* The participant has a personal history of any of the following conditions: syncope of cardiovascular etiology, ventricular arrhythmia of pathological origin or sudden cardiac arrest. Any participant with a history of venous thromboembolism (VTE).
* The participant has active systemic infections or viral load.
* The participant has received an experimental treatment in a clinical trial within the last 30 days or 5 half-lives, whichever is longer.

Participant flow

Outcome results

• Invasive Disease Free Survival (IDFS) (Primary), Median, Months: 150 mg Abemaciclib + Endocrine Therapy NA (NA to NA); Endocrine Therapy NA (NA to NA) (p 0.00957)
• IDFS for Participants With Ki-67 Index ≥20% (Secondary)
• Distant Relapse-Free Survival (DRFS) (Secondary), Median, Months: 150 mg Abemaciclib + Endocrine Therapy NA (NA to NA); Endocrine Therapy NA (NA to NA)
• Overall Survival (OS) (Secondary)
• Pharmacokinetics (PK): Minimum Steady State Concentration (Cmin,ss) of Abemaciclib (Secondary), Geometric mean, Nanograms per milliliter (ng/mL): 150 mg Abemaciclib + Endocrine Therapy 143 +/- 110
• Change From Baseline on the Functional Assessment of Cancer Therapy - Breast (FACT-B) (Secondary)
• Change From Baseline on the Functional Assessment of Cancer Therapy - Endocrine Symptoms (FACT-ES) (Secondary)
• Change From Baseline on the Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) (Secondary)
• Change From Baseline on the EuroQol Five-Dimension Five-Level Questionnaire (EQ-5D-5L) (Secondary)

Adverse events

Time frame: Baseline to 32 Months

Serious adverse events by term

234 more terms not shown.

Other adverse events by term

70 more terms not shown.

519 more sites not listed.

• Results publication: Johnston S, Martin M, O'Shaughnessy J, Hegg R, Tolaney SM, Guarneri V, Del Mastro L, Campone M, Sohn J, Boyle F, Cortes J, Rugo HS, Goetz MP, Hamilton EP, Huang CS, Senkus E, Cicin I, Testa L, Neven P, Huober J, Shao Z, Wei R, Munoz M, San Antonio B, Shahir A, Rastogi P, Harbeck N. Overall survival with abemaciclib in early breast cancer. Ann Oncol. 2026 Feb;37(2):155-165. doi: 10.1016/j.annonc.2025.10.005. Epub 2025 Oct 17. PMID 41110697
• Results publication: Zhang Q, Shen K, Song CG, Ouyang Q, Liu Z, Liu Q, Feng J, Chiu JWY, Tang J, Jiang Z, Tseng LM, Wang X, Yang L, Qian C, Shao Z. Abemaciclib combined with endocrine therapy as adjuvant treatment for hormone-receptor-positive, HER2-, high-risk early breast cancer: 5-year Chinese population analysis of the phase III randomized monarchE study. Ther Adv Med Oncol. 2024 Oct 23;16:17588359241286775. doi: 10.1177/17588359241286775. eCollection 2024. PMID 39463748
• Results publication: Johnston SRD, Rugo HS, Tolaney SM, Munoz Fernandez M, Wei R, Martin M. Abemaciclib plus endocrine therapy for HR+, HER2-, node-positive, high-risk early breast cancer: a plain language summary of the monarchE study. Future Oncol. 2024;20(28):2037-2048. doi: 10.1080/14796694.2024.2362095. Epub 2024 Jul 18. PMID 39023253
• Results publication: Rastogi P, O'Shaughnessy J, Martin M, Boyle F, Cortes J, Rugo HS, Goetz MP, Hamilton EP, Huang CS, Senkus E, Tryakin A, Cicin I, Testa L, Neven P, Huober J, Shao Z, Wei R, Andre V, Munoz M, San Antonio B, Shahir A, Harbeck N, Johnston S. Adjuvant Abemaciclib Plus Endocrine Therapy for Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative, High-Risk Early Breast Cancer: Results From a Preplanned monarchE Overall Survival Interim Analysis, Including 5-Year Efficacy Outcomes. J Clin Oncol. 2024 Mar 20;42(9):987-993. doi: 10.1200/JCO.23.01994. Epub 2024 Jan 9. PMID 38194616
• Results publication: Ganfornina Andrades A, Fenix Caballero S, Salguero Olid A, Alegre Del-Rey Emilio J. Abemaciclib as adjuvant treatment for high-risk early breast cancer. Farm Hosp. 2024 Mar-Apr;48(2):75-78. doi: 10.1016/j.farma.2023.08.006. Epub 2023 Sep 19. English, Spanish. PMID 37735004
• Results publication: Johnston SRD, Toi M, O'Shaughnessy J, Rastogi P, Campone M, Neven P, Huang CS, Huober J, Jaliffe GG, Cicin I, Tolaney SM, Goetz MP, Rugo HS, Senkus E, Testa L, Del Mastro L, Shimizu C, Wei R, Shahir A, Munoz M, San Antonio B, Andre V, Harbeck N, Martin M; monarchE Committee Members. Abemaciclib plus endocrine therapy for hormone receptor-positive, HER2-negative, node-positive, high-risk early breast cancer (monarchE): results from a preplanned interim analysis of a randomised, open-label, phase 3 trial. Lancet Oncol. 2023 Jan;24(1):77-90. doi: 10.1016/S1470-2045(22)00694-5. Epub 2022 Dec 6. PMID 36493792
• Results publication: Toi M, Boyle F, Im YH, Reinisch M, Molthrop D, Jiang Z, Wei R, Sapunar F, Grimes BR, Nabinger SC, Johnston SRD. Adjuvant Abemaciclib Combined with Endocrine Therapy: Efficacy Results in monarchE Cohort 1. Oncologist. 2023 Jan 18;28(1):e77-e81. doi: 10.1093/oncolo/oyac234. PMID 36342342
• Results publication: Martin M, Hegg R, Kim SB, Schenker M, Grecea D, Garcia-Saenz JA, Papazisis K, Ouyang Q, Lacko A, Oksuzoglu B, Reeves J, Okera M, Testa L, Shimizu C, Denduluri N, Adamchuk H, Dakhil S, Wei R, Forrester T, Fernandez MM, Zimmermann A, Headley D, Johnston SRD. Treatment With Adjuvant Abemaciclib Plus Endocrine Therapy in Patients With High-risk Early Breast Cancer Who Received Neoadjuvant Chemotherapy: A Prespecified Analysis of the monarchE Randomized Clinical Trial. JAMA Oncol. 2022 Aug 1;8(8):1190-1194. doi: 10.1001/jamaoncol.2022.1488. PMID 35653145
• Results publication: Perachino M, Poggio F, Arecco L, Blondeaux E, Spinaci S, Marrocco C, Levaggi A, Lambertini M. Update on Pregnancy Following Breast Cancer Diagnosis and Treatment. Cancer J. 2022 May-Jun 01;28(3):176-182. doi: 10.1097/PPO.0000000000000599. PMID 35594464
• Results publication: Polewski MD, Nielsen GB, Gu Y, Weaver AT, Gegg G, Tabuena-Frolli S, Cajaiba M, Hanks D, Method M, Press MF, Gottstein C, Gruver AM. A Standardized Investigational Ki-67 Immunohistochemistry Assay Used to Assess High-Risk Early Breast Cancer Patients in the monarchE Phase 3 Clinical Study Identifies a Population With Greater Risk of Disease Recurrence When Treated With Endocrine Therapy Alone. Appl Immunohistochem Mol Morphol. 2022 Apr 1;30(4):237-245. doi: 10.1097/PAI.0000000000001009. PMID 35384873
• Results publication: Rugo HS, O'Shaughnessy J, Boyle F, Toi M, Broom R, Blancas I, Gumus M, Yamashita T, Im YH, Rastogi P, Zagouri F, Song C, Campone M, San Antonio B, Shahir A, Hulstijn M, Brown J, Zimmermann A, Wei R, Johnston SRD, Reinisch M, Tolaney SM; monarchE Committee Members. Adjuvant abemaciclib combined with endocrine therapy for high-risk early breast cancer: safety and patient-reported outcomes from the monarchE study. Ann Oncol. 2022 Jun;33(6):616-627. doi: 10.1016/j.annonc.2022.03.006. Epub 2022 Mar 23. PMID 35337972
• Results publication: Royce M, Osgood C, Mulkey F, Bloomquist E, Pierce WF, Roy A, Kalavar S, Ghosh S, Philip R, Rizvi F, Mixter BD, Tang S, Pazdur R, Beaver JA, Amiri-Kordestani L. FDA Approval Summary: Abemaciclib With Endocrine Therapy for High-Risk Early Breast Cancer. J Clin Oncol. 2022 Apr 10;40(11):1155-1162. doi: 10.1200/JCO.21.02742. Epub 2022 Jan 27. PMID 35084948
• Results publication: Johnston SRD, Harbeck N, Hegg R, Toi M, Martin M, Shao ZM, Zhang QY, Martinez Rodriguez JL, Campone M, Hamilton E, Sohn J, Guarneri V, Okada M, Boyle F, Neven P, Cortes J, Huober J, Wardley A, Tolaney SM, Cicin I, Smith IC, Frenzel M, Headley D, Wei R, San Antonio B, Hulstijn M, Cox J, O'Shaughnessy J, Rastogi P; monarchE Committee Members and Investigators. Abemaciclib Combined With Endocrine Therapy for the Adjuvant Treatment of HR+, HER2-, Node-Positive, High-Risk, Early Breast Cancer (monarchE). J Clin Oncol. 2020 Dec 1;38(34):3987-3998. doi: 10.1200/JCO.20.02514. Epub 2020 Sep 20. PMID 32954927

• Study Protocol (PDF, 2019-09-18)
• Statistical Analysis Plan (PDF, 2020-06-05)

• Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST), Study director, Eli Lilly and Company

NIH grants: 2016