作者
Nadia Harbeck,Priya Rastogi,Miguel Martín,Sara M. Tolaney,Zhimin Shao,Peter A. Fasching,Chiun‐Sheng Huang,Georgina Garnica Jaliffe,A. Tryakin,Matthew P. Goetz,Hope S. Rugo,Elżbieta Senkus,Laura Testa,Mariette Andersson,Kenji Tamura,Lucia Del Mastro,Guenther G. Steger,Hans Kreipe,Roberto Hegg,Joohyuk Sohn,Valentina Guarneri,Javier Cortés,E. Hamilton,Valérie André,Ran Wei,Susana Barriga,S. Sherwood,Tammy Forrester,Montserrat Muñoz,Ashwin Shahir,Belén San Antonio,Sarah C. Nabinger,Masakazu Toi,Stephen Johnston,Joyce O’Shaughnessy,M.M. Jimenez,Stephen Johnston,F. Boyle,Guenther G. Steger,Patrick Neven,Zefei Jiang,Mario Campone,Jens Huober,Chikako Shimizu,İrfan Çiçin,Andrew Wardley,Sara M. Tolaney,G. Gomez Abuin,J. J. Zarba,Elgene Lim,Peter van ’t Sant,Naishun Liao,Bo Christiansen,Natalja Eigėlienė,J. Martin-Babau,Johannes Ettl,D. Mavroudis,Joanne Chiu,Katalin Boér,R. Nagarkar,Shani Paluch–Shimon,Luca Moscetti,Yoshiatsu Sagara,S.-B. Kim,Rui M. B. Maciel,Vivianne C. G. Tjan‐Heijnen,Reuben Broom,Aleksandra Łacko,M. Schenker,Nikita Volkov,Yoon Sim Yap,Maria A. Coccia-Portugal,J. Ángel García Sáenz,Anne Andersson,Tai-Jong Chao,Erhan Gökmen,Hakan Harputluoğlu,O. Berzoy,Debra A. Patt,Heather L. McArthur,Helen K. Chew,Pavani Chalasani,Peter A. Kaufman,Karen L. Tedesco,Stephanie L. Graff
摘要
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.