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, S. M.; Shao, Z. M.; Fasching, P. A.; Huang, C. S.; Jaliffe, G. G.; Tryakin, A.; Goetz, M. P.; Rugo, H. S.; Senkus, E.; Testa, L.; Andersson, M.; Tamura, K.; Del Mastro, L.; Steger, G. G.; Kreipe, H.; Hegg, R.; Sohn, J.; Guarneri, V.; Cortes, J.; Hamilton, E.; Andre, V.; Wei, R.; Barriga, S.; Sherwood, S.; Forrester, T.; Munoz, M.; Shahir, A.; San Antonio, B.; Nabinger, S. C.; Toi, M.; Johnston, S. R. D. und O'Shaughnessy, J. (2021): Adjuvant abemaciclib combined with endocrine therapy for high-risk early breast cancer: updated efficacy and Ki-67 analysis from the monarchE study. In: Annals of Oncology, Bd. 32, Nr. 12: S. 1571-1581

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 thorn 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 thorn 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.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 0923-7534
• Sprache: Englisch