Over 90% of patients with breast cancer are diagnosed with early breast cancer (EBC). While many patients with HR+ disease will not recur or have distant relapse with standard therapies, up to 30% of patients whose cancer has high risk clinical and/or pathological features may experience distant relapse, many in the first 2 years. Novel treatment options are needed to prevent early recurrences and development of metastases for these patients. Abemaciclib is an oral, continuously dosed CDK4 & 6 inhibitor approved for use in HR+, HER2- advanced breast cancer (ABC). Efficacy and safety of abemaciclib in ABC supported phase III evaluation in the adjuvant setting.
monarchE, an open-label, phase III study, included patients with HR+, HER2-, high risk EBC, who completed primary treatment. Patients with ≥4 positive nodes, or 1-3 nodes and at least one of the following: tumor size ≥5 cm, histologic grade 3, or central Ki-67 ≥20%, were eligible, and randomized (1:1) to abemaciclib (150 mg BID for 2 years) plus endocrine therapy (ET) or ET alone. A prespecified interim analysis was planned at ∼293 IDFS events. The primary endpoint was invasive disease-free survival (IDFS) per STEEP criteria. Secondary endpoints included distant relapse-free survival (DRFS), overall survival, and safety.
5,637 patients were randomized. With 323 IDFS events observed in the intent-to-treat population, positive efficacy required a 2-sided p-value <0.0264. Abemaciclib plus ET demonstrated a statistically significant improvement in IDFS versus ET alone (p=.0096, HR: 0.747, 95% CI: 0.598, 0.932), corresponding to a 25.3% reduction in the risk of an IDFS event. The 2-year IDFS rates were 92.2% vs 88.7%, respectively. A similar improvement was observed for DRFS (HR: 0.717, 95% CI: 0.559, 0.920) with 2-year DRFS rates of 93.6% and 90.3%, respectively. Consistent benefit was seen in all prespecified subgroups. The most frequent AEs were diarrhea, neutropenia and fatigue in the abemaciclib arm and arthralgia, hot flush and fatigue in the control arm. Safety was consistent with the known profile of abemaciclib.
Abemaciclib when combined with ET is the first CDK4 & 6 inhibitor to demonstrate a statistically significant improvement in IDFS in patients with HR+, HER2-, high risk EB.
NCT03155997.
Sarah C Nabinger from Eli Lilly and Company has provided writing support.
Eli Lilly and Company.
Eli Lilly and Company.
S.R.D. Johnston: Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): AstraZeneca; Advisory/Consultancy, Research grant/Funding (institution): Eli Lilly and Company; Puma technology; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Novartis; Pfizer; Speaker Bureau/Expert testimony: Eisai; Speaker Bureau/Expert testimony, Research grant/Funding (institution): Roche/Genentech. N. Harbeck: Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): AstraZeneca; Eli Lilly and Company; Novartis; Pfizer; Shareholder/Stockholder/Stock options: West German Study Group. M. Toi: Honoraria (self), Research grant/Funding (institution): Chugai; Takeda; Pfizer; Eisai; AstraZeneca; Taiho; Nippon Kayaku; Research grant/Funding (institution): Kyowa-Hakko-Kirin; Astellas; AFI technologies; Research grant/Funding (institution), Officer/Board of Directors: JBCRG association; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Shimadzu; Daiichi-Sankyo; Honoraria (self): Eli Lilly and Company; MSD; Honoraria (self): Genomic Health; Novartis; Yakult; Advisory/Consultancy: Konica Minolta; BMS; Athenex Oncology; Officer/Board of Directors: Organisation for Oncology and Translational Research; Kyoto Breast cancer Research Network. M. Martin: Advisory/Consultancy, Speaker Bureau/Expert testimony: AstraZeneca; Amgen; Pfizer; Advisory/Consultancy: Taiho Oncology; PharmaMar; Eli Lilly and Company; Daiichi Sankyo; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Roche/Genentech; Novartis; Advisory/Consultancy, Research grant/Funding (institution): PUMA; M. Campone: Advisory/Consultancy, Fees to the Institution: AstraZeneca; Sanofi; Servier; AbbVie; ACCORD; Pfizer; Advisory/Consultancy, Speaker Bureau/Expert testimony: Novartis; Advisory/Consultancy: Eli Lilly and Company; GT1. E. Hamilton: Speaker Bureau/Expert testimony, Research grant/Funding (institution), speaker's bureau (no personal compensation accepted): Genentech/Roche; Advisory/Consultancy, Research grant/Funding (institution), advisory board (no personal compensation accepted): Eli Lilly and Company; Pfizer; Novartis; Mersana; Advisory/Consultancy: Flatiron Health; Advisory/Consultancy, Research grant/Funding (institution), consulting (no personal compensation accepted): Cascadian Therapeutics; Daiichi; AstraZeneca; Silverback Therapeutics; Black Diamond; Research grant/Funding (institution): Hutchinson MediPharma; OncoMed; MedImmune; StemCentrx; AbbVie; Curis; Verastem; Zymeworks; Syndax; Lycera; Rgenix; TapImmune; BerGenBio; Tesaro; Medivation; Kadmon; Boehringer Ingelheim; Eisai; H3 Biomedicine; Radius Health; Acerta; Takeda; Macrogenics; Immunomedics; FujiFilm; Effector; Syros; Unum; Sutro; Aravive; Deciphera; Clovis; Sermonix; Zenith; Arvinas; ArQule; Torque; Harpoon; Fochon; Orinove; Molecular Template; Seattle Genetics. J. Sohn: Research grant/Funding (institution): MSD; Roche; Novartis; AstraZeneca; Eli Lilly and Company; Pfizer; Bayer; GSK; CONTESSA; Daiichi Sankyo. V. Guarneri: Advisory/Consultancy, Speaker Bureau/Expert testimony: Eli Lilly and Company; Novartis; Advisory/Consultancy, Research grant/Funding (institution): Roche. J. Cortes: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Roche; Honoraria (self), Advisory/Consultancy: Celgene; Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Advisory/Consultancy: Cellestia; Biothera Pharmaceutical; Merus; Seattle Genetics; Erytech; Athenex; Polyphor; Servier; GSK; Leuko; Bioasis; Clovis Oncology; Boehringer Ingelheim; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Daiichi Sankyo; Honoraria (self), Advisory/Consultancy: Eli Lilly and Company; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Merck; Sharp&Dohme; Honoraria (self), Travel/Accommodation/Expenses: Novartis; Honoraria (self), Research grant/Funding (institution), Travel/Accommodation/Expenses: Eisai; Pfizer; Honoraria (self): Samsung Bioepis; Research grant/Funding (institution): Ariad pharmaceuticals; Baxalta GMBH/Servier Affaires; Bayer healthcare; F.Hoffman-La Roche; Guardanth health; Piqur Therapeutics; Puma C; Queen Mary University of London; Shareholder/Stockholder/Stock options: MedSIR. P. Neven: Honoraria (self), Research grant/Funding (institution), Travel/Accommodation/Expenses: Eli Lilly and Company. F. Boyle: Honoraria (self), Advisory/Consultancy: Roche; Pfizer; Eli Lilly and Company; Novartis. I. Smith: Full/Part-time employment, was a full time employee of Eli Lilly during the conduct of the study: Eli Lilly and Company. M. Frenzel; R. Wei; J. Cox: Shareholder/Stockholder/Stock options, Full/Part-time employment: Eli Lilly and Company. D. Headley: Shareholder/Stockholder/Stock options, Full/Part-time employment: Eli Lilly and Company; Shareholder/Stockholder/Stock options: Novartis; Takeda; Varian Medical systems; Utah Medical Products; Zoetis; Bayer; Roche; Evgen; AstraZeneca; Johnston&Johnston; Pfizer; Varex Imaging; Zimmer BioMet; Amgen; Chugai Pharma; Merck. J. O'Shaughnessy: Honoraria (self), Advisory/Consultancy: AbbVie Inc; Agendia; Amgen Biotechnology; AstraZeneca; Bristol-Myers Squibb; Celgene Corporation; Eisai; Genentech; Genomic Health; GRAIL; Immunomedics; Heron Therapeautics; Ipsen Biopharmaceuticals; Jounce Therapeutics; Eli Lilly and Company; Merck; Myriad; Novartis; Ondonate Therapeutics; Pfizer; Puma Biotechnology; Prime Oncology; Roche; Seattle Genetics; Takeda; Syndax Pharmaceuticals. P. Rastogi: Travel/Accommodation/Expenses: AstraZeneca; Genentech/Roche; Eli Lilly and Company. All other authors have declared no conflicts of interest.