Adjuvant abemaciclib combined with endocrine therapy for high-risk early breast cancer: updated efficacy and Ki-67 analysis from the monarchE study

Harbeck N, Rastogi P, Martin M, Tolaney SM, Shao ZM, Fasching P, Huang CS, Jaliffe GG, Tryakin A, Goetz MP, Rugo HS, Senkus E, Testa L, Andersson M, Tamura K, Del Mastro L, Steger GG, Kreipe H, Hegg R, Sohn J, Guarneri V, Cortés J, Hamilton E, André V, Wei R, Barriga S, Sherwood S, Forrester T, Munoz M, Shahir A, San Antonio B, Nabinger SC, Toi M, Johnston SR, O'Shaughnessy J, Jimenez MM, Johnston S, Boyle F, Neven P, Jiang Z, Campone M, Huober J, Shimizu C, Cicin I, Wardley A, Abuin GG, Zarba J, Lim E, Sant P, Liao N, Christiansen B, Eigeliene N, Martin-Babau J, Ettl J, Mavroudis D, Chiu J, Boer K, Nagarkar R, Paluch-Shimon S, Moscetti L, Sagara Y, Kim SB, Maciel MM, Tjan-Heijnen V, Broom R, Lacko A, Schenker M, Volkov N, Sim Yap Y, Coccia-Portugal M, Ángel García Sáenz J, Andersson A, Chao TY, Gokmen E, Harputluoglu H, Berzoy O, Patt D, McArthur H, Chew H, Chalasani P, Kaufman P, Tedesco K, Graff SL (2021)

Publication Type: Journal article

Publication year: 2021

Journal

Book Volume: 32

Pages Range: 1571-1581

Journal Issue: 12

DOI: 10.1016/j.annonc.2021.09.015

Abstract

Background: Adjuvant abemaciclib combined with endocrine therapy (ET) previously demonstrated clinically meaningful improvement in invasive disease-free survival (IDFS) and distant relapse-free survival (DRFS) in hormone receptor-positive, human epidermal growth factor receptor 2-negative, node-positive, high-risk early breast cancer at the second interim analysis, however follow-up was limited. Here, we present results of the prespecified primary outcome analysis and an additional follow-up analysis. Patients and methods: This global, phase III, open-label trial randomized (1: 1) 5637 patients to adjuvant ET for ≥5 years ± abemaciclib for 2 years. Cohort 1 enrolled patients with ≥4 positive axillary lymph nodes (ALNs), or 1-3 positive ALNs and either grade 3 disease or tumor ≥5 cm. Cohort 2 enrolled patients with 1-3 positive ALNs and centrally determined high Ki-67 index (≥20%). The primary endpoint was IDFS in the intent-to-treat population (cohorts 1 and 2). Secondary endpoints were IDFS in patients with high Ki-67, DRFS, overall survival, and safety. Results: At the primary outcome analysis, with 19 months median follow-up time, abemaciclib + ET resulted in a 29% reduction in the risk of developing an IDFS event [hazard ratio (HR) = 0.71, 95% confidence interval (CI) 0.58-0.87; nominal P = 0.0009]. At the additional follow-up analysis, with 27 months median follow-up and 90% of patients off treatment, IDFS (HR = 0.70, 95% CI 0.59-0.82; nominal P < 0.0001) and DRFS (HR = 0.69, 95% CI 0.57-0.83; nominal P < 0.0001) benefit was maintained. The absolute improvements in 3-year IDFS and DRFS rates were 5.4% and 4.2%, respectively. Whereas Ki-67 index was prognostic, abemaciclib benefit was consistent regardless of Ki-67 index. Safety data were consistent with the known abemaciclib risk profile. Conclusion: Abemaciclib + ET significantly improved IDFS in patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative, node-positive, high-risk early breast cancer, with an acceptable safety profile. Ki-67 index was prognostic, but abemaciclib benefit was observed regardless of Ki-67 index. Overall, the robust treatment benefit of abemaciclib extended beyond the 2-year treatment period.

Authors with CRIS profile

Involved external institutions

Eli Lilly and Company United States (USA) (US) Kyoto University Hospital / 京都大学医学部附属病院 Japan (JP) Royal Marsden Hospital / The Royal Marsden NHS Foundation Trust United Kingdom (GB) University of Pittsburgh United States (USA) (US) Ospedale Policlinico San Martino Italy (IT) Vall d'Hebron University Hospital / Hospital Universitari Vall d'Hebron Spain (ES) Baylor University Medical Center United States (USA) (US) Klinikum der Universität München Germany (DE) Hospital General Universitario Gregorio Marañón Spain (ES) Dana–Farber Cancer Institute United States (USA) (US) Fudan University / 复旦大学 China (CN) National Taiwan University (NTU) Taiwan (TW) Grupo México Camino S.C. Mexico (MX) N.N. Blokhin Russian Cancer Research Center / Российский онкологический научный центр им. Н. Н. Блохина Russian Federation (RU) Mayo Clinic United States (USA) (US) University of California San Francisco (UCSF) United States (USA) (US) Medical University Gdansk / Gdański Uniwersytet Medyczny Poland (PL) IDOR Instituto D'Or de Pesquisa e Ensino Brazil (BR) Rigshospitalet Denmark (DK) National Cancer Center Hospital Japan (JP) Medizinische Universität Wien Austria (AT) Medizinische Hochschule Hannover (MHH) / Hannover Medical School Germany (DE) Yonsei University Health System (YUHS) Korea, Republic of (KR) University of Padua / Universita degli Studi di Padova Italy (IT) Sarah Cannon Research Institute (SCRI) United States (USA) (US)

How to cite

APA:

Harbeck, N., Rastogi, P., Martin, M., Tolaney, S.M., Shao, Z.M., Fasching, P.,... Graff, S.L. (2021). Adjuvant abemaciclib combined with endocrine therapy for high-risk early breast cancer: updated efficacy and Ki-67 analysis from the monarchE study. Annals of Oncology, 32(12), 1571-1581. https://doi.org/10.1016/j.annonc.2021.09.015

MLA:

Harbeck, N., et al. "Adjuvant abemaciclib combined with endocrine therapy for high-risk early breast cancer: updated efficacy and Ki-67 analysis from the monarchE study." Annals of Oncology 32.12 (2021): 1571-1581.

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