Adjuvant abemaciclib combined with endocrine therapy for high-risk early breast cancer: updated efficacy and Ki-67 analysis from the monarchE study
Authors: N. Harbeck, P. Rastogi, M. Martin, S.M. Tolaney, Z.M. Shao, P.A. Fasching, C.S. Huang, G.G. Jaliffe, A. Tryakin, M.P. Goetz, H.S. Rugo, E. Senkus, L. Testa, M. Andersson, K. Tamura, L. Del Mastro, G.G. Steger, H. Kreipe, R. Hegg, J. Sohn, V. Guarneri, J. Cortés, E. Hamilton, V. André, R. Wei, S. Barriga, S. Sherwood, T. Forrester, M. Munoz, A. Shahir, B. San Antonio, S.C. Nabinger, M. Toi, S.R.D. Johnston, J. O’Shaughnessy, M.M. Jimenez, S. Johnston, F. Boyle, G.G. Steger, P. Neven, Z. Jiang, M. Campone, J. Huober, C. Shimizu, I. Cicin, A. Wardley, S.M. Tolaney, G.G. Abuin, J. Zarba, E. Lim, P. Sant, N. Liao, B. Christiansen, N. Eigeliene, J. Martin-Babau, J. Ettl, D. Mavroudis, J. Chiu, K. Boer, R. Nagarkar, S. Paluch-Shimon, L. Moscetti, Y. Sagara, S.-B. Kim, M.M. Maciel, V. Tjan-Heijnen, R. Broom, A. Lacko, M. Schenker, N. Volkov, Y. Sim Yap, M. Coccia-Portugal, J. Ángel García Sáenz, A. Andersson, T.-Y. Chao, E. Gokmen, H. Harputluoglu, O. Berzoy, D. Patt, H. McArthur, H. Chew, P. Chalasani, P. Kaufman, K. Tedesco, S.L. Graff
Journal: Annals of Oncology (2021)

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.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.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.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.