Primary outcome analysis of invasive disease-free survival for monarchE: abemaciclib plus adjuvant endocrine therapy for high-risk early breast cancer

Goal monarchE (phase 3, open-label) evaluated abemaciclib+endocrine therapy (ET) vs ET-alone in node-positive, HR+, HER2-, high-risk early breast cancer that resulted in a statistically significant improvement in invasive disease-free survival (IDFS) at a pre-planned interim analysis.

Material and method Following the positive interim analysis, patients continued to be followed for IDFS, distant recurrence and overall survival. 5,637 patients were randomized (1:1) to standard-of-care adjuvant ET with/without abemaciclib (150mg BD for 2 years). Patients with ≥4 positive nodes, or 1-3 nodes and either grade3 disease, tumor size≥5 cm, or central Ki-67≥20% were eligible. We present results of the primary outcome IDFS analysis which was planned after ~390 IDFS events.

Results At the primary outcome analysis, median follow-up of ~19 months (mo) in both arms. With 395 IDFS events observed, abemaciclib+ET continued to demonstrate superior IDFS vs ET-alone (p=.0009; HR=0.713). Two-year IDFS rates were 92.3% (abemaciclib+ET) and 89.3% (ET-alone). With 324 distant relapse-free survival (DRFS) events observed, abemaciclib+ET improved DRFS vs ET-alone (p=.0009; HR=.687). Two-year DRFS rates were 93.8% (abemaciclib+ET) and 90.8% (ET-alone).A key secondary endpoint was efficacy in patients with centrally assessed high Ki-67 (≥20%) (Ki-67H, n=2498). Abemaciclib+ET demonstrated superior IDFS vs ET-alone (p=.0111; HR=.691) and 2-year IDFS rates of 91.6% and 87.1%, respectively.

Summary Abemaciclib+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≥20%.

Interessenkonflikt

Joyce O’Shaughnessy Honoraria for consulting and advisory boards: AbbVie Inc., Agendia, Amgen Biotechnology, AstraZeneca, Bristol-Myers Squibb, Celgene Corporation, Eisai, Genentech, Genomic Health, GRAIL, Immunomedics, Heron Therapeautics, Ipsen Biopharmaceuticals, Jounce Therapeutics, Lilly, Merck, Myriad, Novartis, Ondonate Therapeutics, Pfizer, Puma Biotechnology, Prime Oncology, Roche, Seattle Genetics, Syndax Pharmaceuticals, Takeda Stephen Johnston Consulting or Advisory Role - Lilly; Novartis; Pfizer; Puma Biotechnology Speakers´ Bureau - AstraZeneca; Eisai; Lilly; Novartis; Pfizer; Roche Research Funding - Pfizer (Inst); Puma Biotechnology (Inst) Nadia Harbeck Consulting Fees (e.g. advisory boards): Astra Zeneca, Lilly, Novartis, Pfizer, Fees for Non-CME Services Received Directly from Commercial Interest or their Agents (e.g. speakers´ bureaus): Astra Zeneca, Lilly, Novartis, Pfizer, Contracted Research: All to institution, Ownership Interest (stock, stock options, or other ownership interest excluding diversified mutual funds) - West German Study Group (WSG) (minority ownership) Masakazu Toi Honoraria - AstraZeneca; Chugai Pharma; Daiichi Sankyo; Eisai; Genomic Health; Konica Minolta; Kyowa Hakko Kirin; Lilly; Novartis; Pfizer; Shimadzu; Taiho Pharmaceutical; TAKEDA; Yakult Pharmaceutical Consulting or Advisory Role - Daiichi Sankyo; Konica Minolta; Kyowa Hakko Kirin Speakers´ Bureau - AstraZeneca; Lilly; Pfizer Research Funding - AFI technology; Astellas Pharma; AstraZeneca; Chugai Pharma; Daiichi Sankyo; Eisai; Japan Breast Cancer Research Group; Kyoto Breast cancer Research Network; Nippon Kayaku; Ono Pharmaceutical; Pfizer; Shimadzu; Taiho Pharmaceutical Patents, Royalties, Other Intellectual Property - JP 2017-143763 WO2017/131162A1 (Inst); PCT/JP2016/004374 (Inst) Travel, Accommodations, Expenses - Eisai; Takeda Other Relationship - Japan Breast Cancer Research Group; Japan Breast Cancer Research Group; Kyoto Breast Cancer Research Network; Organization for Oncology and Translational Research Young-Hyuck Im No Relationships to Disclose Mattea Reinisch Consulting fees: Eli Lilly and Company, MSD, Astrazeneca, Roche, Novartis, Sonatex Travel support from Novartis, Pfizer. Zhi Min Shao No Relationships to Disclose Pirkko Liisa Kellokumpu Lehtinen No Relationships to Disclose Chiun-Sheng Huang Consulting fees: Eli Lilly and Company, Roche, Pfizer, Amgen Fees for Non-CME Services Received Directly from Commercial Interest or their Agents: Amgen, Pfizer, Novartis, Roche Contracted research: Eli Lilly and Company, Pfizer, Novartis, Astrazeneca, EirGenix, OBI Pharma, MSD, Daiichi Sankyo, Roche Travel and accommodations support: AstraZeneca, Pfizer, Roche, Amgen. Alexey Tryakin Consulting or Advisory Role - BioCad; Bristol-Myers Squibb; Eisai; Roche/Genentech Speakers´ Bureau - Amgen; Bayer Health; BioCad; Bristol-Myers Squibb; Eisai; Lilly; Merck Serono; Sanofi Travel, Accommodations, Expenses - Bayer; BioCad; Novartis; Veropharm Matthew Goetz Personal fees: Genomic Health, Consulting fees to Mayo: Lilly, Biovica, Novartis, Sermonix, Context Pharm Grants: Pfizer, Lilly, Biotheranostics Hope Rugo Funding for Sponsored studies to UCSF: Pfizer, Novartis, Lilly, Genentech/Roche, Macrogenics, Merck, Eisai, OBI, Odonate, Daiichi, Seattle Genetics, Immunomedics, Travel Support for educational meetings: Puma, Mylan, Amgen, AstraZeneca, Daiichi, Merck, Macrogenics, Pfizer Elzbieta Senkus Consulting fees: Amgen, AstraZeneca, Clinigen, Egis, Eli Lilly and Company, Genomic Health, Novartis, Pfizer, Pierre Fabre, Roche, Sandoz, TLC Biopharmaceuticals Fees for Non-CME Services Received Directly from Commercial Interest or their Agents: Egis, Genomic Health, Novartis, Pfizer, Pierre Fabre, Roche Contracted research: Amgen, AstraZeneca, Boehringer, Eli Lilly and Company, Merck, Novartis, Pfizer, Roche, Samsung Ownership interest: Eli Lilly and Company Travel support:Amgen, AstraZeneca, Egis, Novartis, Pfizer, Roche. Laura Testa Consulting or Advisory Role - Amgen; Lilly; Lilly; MSD Oncology, Genomic Health Fees for Non-CME Services Received Directly from Commercial Interest or their Agents:Lilly, Novartis, Pfizer, Roche, Libbs Travel, Accommodations, Expenses - Libbs; Pfizer; United Medical Michael Andersson No Relationships to Disclose Kenji Tamura Contracted research: Eli Lilly and Company, MSD, AstraZeneca, Pfizer, Chugai, Eisai Guenther Steger Consulting fees: Lilly, AstraZeneca, Roche, Pfizer, TEVA, Amgen Travel support: Eli Lilly and Company, Roche, Pfizer Lucia Del Mastro Consulting fees: Roche, Novartis, Pfizer, Eli Lilly and Company, Pierre Fabre, Seattle Genetics, MSD, Astrazeneca Fees for Non-CME Services Received Directly from Commercial Interest or their Agents: Roche, Novartis, Eli Lilly and Company, Eisai Joanne Cox Employment - Lilly Stock and Other Ownership Interests – Lilly Tammy Forrester Employment - Lilly Stock and Other Ownership Interests – Lilly Sarah Sherwood Employment - Lilly Stock and Other Ownership Interests – Lilly Xuelin Li Employment - Lilly Stock and Other Ownership Interests – Lilly Ran Wei Employment - Lilly Stock and Other Ownership Interests – Lilly Miguel Martin Reports grants and personal fees: Roche, Novartis, Puma, Lilly, Gsk, Astrazeneca, Amgen, Taiho Oncology, Pharmamar, Pfizer, Daiichi Sanyo Priya Rastogi Travel and accommodations - AstraZeneca, Genentech/Roche, and Lilly.

Publication History

Article published online:
01 June 2021