Joyce O’Shaughnessy, MD1; Stephen Johnston, PhD, FRCP, MA2; Nadia Harbeck, MD, PhD3; Masakazu Toi, MD, PhD4; Young-Hyuck Im, MD5; Mattea Reinisch, MD6; Zhi Min Shao, MD7; Pirkko-Liisa Kellokumpu-Lehtinen, MD, PhD8; ChiunSheng Huang, MD, PhD, MPH9; Alexey Tryakin, MD, DSci10; Matthew Goetz, MD11; Hope Rugo, MD, FASCO12; Elzbieta Senkus-Konefka, MD, PhD13; Laura Testa, MD14; Michael Andersson, MD15; Kenji Tamura, MD, PhD16; Guenther Steger, MD17; Lucia Del Mastro, MD18; Joanne Cox, MD19; Tammy Forrester, MS19; Sarah Sherwood, PhD19; Xuelin Li, PhD19; Ran Wei, PhD19, Miguel Martin, MD, PhD20; Priya Rastogi, MD21
1Baylor University Medical Center, Texas Oncology, US Oncology, Dallas, TX
2Royal Marsden NHS Foundation Trust, London, UK
3Breast Center, Dept OB&GYN, LMU University Hospital, Munich, Germany
4Kyoto University Hospital, Kyoto, Japan
5Samsung Medical Center, Seoul, Republic of Korea
6Brustzentrum Kliniken Essen-Mitte, Essen, Germany
7Fudan University Shanghai Cancer Center, Shanghai, China
8Tampere University Hospital TAYS, Tampere, Finland
9National Taiwan University Hospital, Taipei, Taiwan
10N.N. Blokhin Russian Cancer Research Center, Moscow, Russian Federation
11Mayo Clinic, Rochester, MN
12University of California San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, CA
13Medical University of Gdańsk, Gdańsk, Poland
14IDOR (Institute D’Or for Research and Education), Sao Paulo, Brazil
15Rigshospitalet, Copenhagen, Denmark
16Department of Breast and Medical Oncology, National Cancer Center Hospital, Tokyo, Japan
17Medical University of Vienna, Vienna, Austria
18Breast Unit, IRCCS Ospedale Policlinico, Università di Genova, Italy
19Eli Lilly and Company, Indianapolis, IN
20Hospital General Universitario Gregorio Marañon, Universidad Complutense, Ciberonc, GEICAM, Madrid, Spain
21University of Pittsburgh, NSABP Foundation, Pittsburgh, PA
The open-label phase 3 monarchE trial (NCT03155997) evaluated abemaciclib (Verzenio) plus endocrine therapy (ET) versus ET alone in node-positive, hormone receptor–positive, HER2-negative (HR+/HER2-), high-risk early breast cancer that resulted in a statistically significant improvement in invasive disease-free survival (IDFS) at a preplanned interim analysis.
Materials and methods
Following the positive interim analysis, patients continued to be followed for IDFS, distant recurrence, and overall survival. Patients (n = 5637) were randomized (1:1) to standard-of-care adjuvant ET with/without abemaciclib (150 mg twice daily for 2 years). Patients with 4 or more positive nodes, or 1 to 3 nodes and either grade 3 disease, tumor size of 5 cm or more, or central Ki-67 of 20% or greater were eligible. We present results of the primary outcome IDFS analysis, which was planned after about 390 IDFS events.
At the primary outcome analysis, median follow-up was about 19 months in both arms. With 395 IDFS events observed, abemaciclib plus ET continued to demonstrate superior IDFS versus ET alone (P = .0009; HR, 0.713; 95% CI, 0.583-0.871). Two-year IDFS rates were 92.3% (95% CI, 90.9%-93.5%; abemaciclib plus ET) and 89.3% (95% CI, 87.7%-90.7%; ET alone). With 324 distant relapse-free survival (DRFS) events observed, abemaciclib plus ET improved DRFS versus ET alone (HR, 0.687; 95% CI, 0.551-0.858; P = .0009). Two-year DRFS rates were 93.8% (95% CI, 92.6%-94.9%; abemaciclib plus ET) and 90.8% (95% CI, 89.3%-92.1%; ET alone).
A key secondary end point was efficacy in patients with centrally assessed high Ki-67 (≥ 20%; Ki-67H, n = 2498). Abemaciclib plus ET demonstrated superior IDFS versus ET alone (HR, 0.691; 95% CI, 0.519-0.920; P = .0111) and 2-year IDFS rates were 91.6% (95% CI, 89.4%-93.4%) and 87.1% (95% CI, 84.3%-89.5%), respectively. Abemaciclib plus ET demonstrated superior DRFS versus ET alone (HR, 0.609; 95% CI, 0.445-0.833; P = .0018) and 2-year DRFS rates were 93.6% (95% CI, 91.6%-95.1%) and 88.5% (95% CI, 85.7%-90.7%), respectively. An improvement in DRFS treatment effect was also observed in the Ki-67H population. Safety was consistent both with the results at the interim IDFS analysis and the known safety profile of abemaciclib.
Abemaciclib plus ET demonstrated a clinically meaningful improvement in IDFS in the study population with a statistically significant improvement in IDFS in patients with central Ki-67 of 20% or greater. Reused with permission SABCS® 2020.
Joyce O’Shaughnessy: Received honoraria for consulting: AbbVie Inc, Agendia, Amgen Biotechnology, AstraZeneca, Bristol Myers Squibb, Celgene Corporation, Eisai, Genentech, Genomic Health, GRAIL, Heron Therapeutics, Immunomedics, Ipsen Biopharmaceuticals, Jounce Therapeutics, Lilly, Merck, Myriad, Novartis, Odonate Therapeutics, Pfizer, Prime Oncology, Puma Biotechnology, Roche, Seattle Genetics, Syndax Pharmaceuticals, Takeda; Received honoraria for advisory boards: AbbVie, Agendia, Amgen, AstraZeneca, Bristol Myers Squibb, Celgene, Eisai, Genentech, Genomic Health, GRAIL, Heron, Immunomedics, Ipsen, Jounce, Lilly, Merck, Myriad, Novartis, Odonate, Pfizer, Puma, Prime Oncology, Roche.
Mattea Reinisch: Received honoraria and travel support from: AstraZeneca, Celgene, Lilly, MSD, Novartis, Pfizer, Roche, Somatex.
Laura Testa: Speaker at scientific events supported by: Amgen, Libbs, Lilly, Novartis, Pfizer Roche; Advisory Boards: Amgen, Lilly, MSD, Novartis; Educational support for meetings: Libbs, Pfizer, United Medical.
Miguel Martin: Received research grants from Novartis, Puma, Roche; Consulting/advisory fees from Amgen, AstraZeneca, Daiichi Sankyo, Eli Lilly, Novartis, Pfizer, PharmaMar, Puma, Roche/Genentech, Taiho Oncology; Speakers’ honoraria from Amgen, AstraZeneca, Lilly, Novartis, Pfizer, Roche/Genentech.
Elzbieta Senkus-Konefka: Honoraria: Amgen, AstraZeneca, Clinigen, Egis, Eli Lilly, Genomic Health, Novartis, Oncompass Medicine, Pfizer, Pierre Fabre, Roche, Sandoz, TLC Biopharmaceuticals; Travel support: Amgen, AstraZeneca, Egis, Novartis, Pfizer, Roche; Clinical research: Amgen, AstraZeneca, Eli Lilly, Novartis, Pfizer, Roche, Samsung; Stock: Eli Lilly, Pfizer.
Pirkko-Liisa Kellokumpu-Lehtinen: Consulting or advisory role: BMS, Merck; Research Funding: Lilly.
Lucia Del Mastro: Honoraria: Lilly, MSD Oncology, Novartis, Roche; Consulting or advisory role: AstraZeneca, Daiichi Sankyo, Eisai, Genomic Health, Ipsen, Lilly, MSD, Novartis, Pfizer, Pierre Fabre, Roche, Seattle Genetics; Travel, accommodations, expenses: Celgene, Pfizer, Roche.
Masakazu Toi: Grants and personal fees: Astellas, AstraZeneca, C & C Res Lab, Chugai, Daiichi Sankyo, Eisai, Eli Lilly, Genomic Health, JBCRG association, Konica Minolta, Kyowa Hakko Kirin, MSD, Novartis, Pfizer, Taiho, Takeda, outside the submitted work; Board of directors: JBCRG association, Kyoto Breast Cancer Research Network, Organisation for Oncology and Translational Research.
Tammy Forrester, Sarah Sherwood, Xuelin Li, Ran Wei: Lilly employees with Lilly stock.
Priya Rastogi: Travel support: AstraZeneca, Eli Lilly and Company, Genentech/Roche; Advisory board: Genentech/Roche (uncompensated).