LBA5_PR - Abemaciclib in high risk early breast cancer

Background

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.

Methods

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.

Results

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.

Conclusions

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 EBC.

Clinical trial identification

NCT03155997.

Editorial acknowledgement

Writing assistance provided by Sarah C. Nabinger (Eli Lilly and Company).

Legal entity responsible for the study

Eli Lilly and Company.

Funding

Eli Lilly and Company.

Disclosure

S.R.D. Johnston: Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (self): AstraZeneca; Advisory/Consultancy, Research grant/Funding (self): Eli Lilly and Company; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (self): Novartis; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (self): Pfizer; Advisory/Consultancy, Research grant/Funding (self): Puma Biotechnology; Speaker Bureau/Expert testimony: Eisai; Speaker Bureau/Expert testimony, Research grant/Funding (self): Roche/Genentech. N. Harbeck: Honoraria (self), Advisory/Consultancy: Eli Lilly and Company; Honoraria (self), Advisory/Consultancy: AstraZeneca; Honoraria (self), Advisory/Consultancy: Novartis; Honoraria (self), Advisory/Consultancy: Pfizer. M. Toi: Honoraria (self), Research grant/Funding (institution): Chugai; Honoraria (self), Research grant/Funding (institution): Takeda; Honoraria (self), Research grant/Funding (institution): Pfizer; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Kyowa-Hakko-Kirin; Honoraria (self), Research grant/Funding (institution): Taiho; Research grant/Funding (institution), Officer/Board of Directors: JBCRG Association; Honoraria (self), Research grant/Funding (institution): Eisai; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Daiichi-Sankyo; Honoraria (self), Research grant/Funding (institution): AstraZeneca; Honoraria (self): Eli Lilly and Company; Honoraria (self): MSD; Honoraria (self): Genomic Health; Honoraria (self): Novartis; Honoraria (self), Honorarium for advisory meeting: Konica Minolta; Research grant/Funding (institution): Astellas; Honoraria (self), Honorarium for advisory meeting: BMS; Honoraria (self), Research grant/Funding (institution): Shimadzu; Honoraria (self): Yakult; Honoraria (self), Research grant/Funding (institution): Nippon Kayaku; Research grant/Funding (institution): AFI Technologies; Advisory/Consultancy: Athenex Oncology; Officer/Board of Directors: Organization for Oncology and Translational Research; Officer/Board of Directors: Kyoto Breast Cancer Research Network. M. Martin: Honoraria (self), Research grant/Funding (self), Personal fees: Roche; Honoraria (self), Research grant/Funding (self), Personal fees: Novartis; Honoraria (self), Research grant/Funding (self), Personal fees: Puma; Honoraria (self), Travel/Accommodation/Expenses, Personal fees: Eli Lilly and Company; Honoraria (self), Personal fees: GSK; Honoraria (self), Personal fees: AstraZeneca; Honoraria (self), Personal fees: Amgen; Honoraria (self), Personal fees: Taiho Oncology; Honoraria (self), Personal fees: PharmaMar; Honoraria (self), Personal fees: Pfizer; Honoraria (self), Personal fees: Daiichi Sanyo. M. Campone: Advisory/Consultancy, Fees to the institution: AstraZeneca; Advisory/Consultancy, Fees to the institution: Sanofi; Advisory/Consultancy, Fees to the institution: Servier; Advisory/Consultancy, Fees to the institution: AbbVie; Honoraria (self), Advisory/Consultancy: Eli Lilly and Company; Advisory/Consultancy, fees to the institution: Accord; Advisory/Consultancy, Speaker Bureau/Expert testimony: Novartis; Advisory/Consultancy, Fees to the institution: Pfizer; Advisory/Consultancy: GT1. E.P. Hamilton: Advisory/Consultancy, Research grant/Funding (institution), Advisory board (no Personal compensation accepted): Eli Lilly and Company; Advisory/Consultancy, Research grant/Funding (institution), Advisory board (no Personal compensation accepted): Pfizer; Speaker Bureau/Expert testimony, Research grant/Funding (institution), Speaker's bureau (no Personal compensation accepted): Genentech/Roche; Advisory/Consultancy: Flatiorn Health; Advisory/Consultancy, Research grant/Funding (institution), Consulting (no Personal compensation accepted): Cascadian Therapeutics; Research grant/Funding (institution): Hutchinson MediPharma; Research grant/Funding (institution): OncoMed; Research grant/Funding (institution): MedImmune; Research grant/Funding (institution): StemCentrx; Research grant/Funding (institution): AbbVie; Research grant/Funding (institution): Curis; Research grant/Funding (institution): Verastem; Research grant/Funding (institution): Zymeworks; Research grant/Funding (institution): Syndax; Research grant/Funding (institution): Lycera; Research grant/Funding (institution): Rgenix; Advisory/Consultancy, Research grant/Funding (institution), Consulting (no Personal compensation accepted): Novartis; Advisory/Consultancy, Research grant/Funding (institution), Consulting (no Personal compensation accepted): Mersana; Research grant/Funding (institution): Taplmmune; Research grant/Funding (institution): BerGenBio; Research grant/Funding (institution): Tesaro; Research grant/Funding (institution): Medivation; Research grant/Funding (institution): Kadmon; Research grant/Funding (institution): Boehringer Ingelheim; Research grant/Funding (institution): Eisai; Research grant/Funding (institution): H3 Biomedicine; Research grant/Funding (institution): Radius Health; Research grant/Funding (institution): Acerta; Research grant/Funding (institution): Takeda; Research grant/Funding (institution): Macrogenics; Research grant/Funding (institution): Immunomedics; Research grant/Funding (institution): FujiFilm; Research grant/Funding (institution): Effector; Research grant/Funding (institution): Syros; Research grant/Funding (institution): Unum; Research grant/Funding (institution): Sutro; Research grant/Funding (institution): Aravive; Research grant/Funding (institution): Deciphera; Research grant/Funding (institution): Clovis; Research grant/Funding (institution): Sermonix; Research grant/Funding (institution): Zenith; Research grant/Funding (institution): Arvinas; Research grant/Funding (institution): ArQule; Research grant/Funding (institution): Torque; Research grant/Funding (institution): Harpoon; Research grant/Funding (institution): Fachon; Research grant/Funding (institution): Orinove; Research grant/Funding (institution): Molecular Template; Research grant/Funding (institution): Seattle Genetics; Advisory/Consultancy, Research grant/Funding (institution), consulting (no Personal compensation accepted): Daiichi; Advisory/Consultancy, Research grant/Funding (institution), consulting (no Personal compensation accepted): AstraZeneca; Advisory/Consultancy, Research grant/Funding (institution), consulting (no Personal compensation accepted): Silverback Therapeutics; Advisory/Consultancy, Research grant/Funding (institution), consulting (no Personal compensation accepted): Black Diamond. J. Sohn: Research grant/Funding (institution): MSD; Research grant/Funding (institution): Roche; Research grant/Funding (institution): Novartis; Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): Eli Lilly and Company; Research grant/Funding (institution): Pfizer; Research grant/Funding (institution): Bayer; Research grant/Funding (institution): GSK; Research grant/Funding (institution): CONTESSA; Research grant/Funding (institution): Daiichi Sankyo. V. Guarneri: Advisory/Consultancy, Speaker Bureau/Expert testimony: Eli Lilly and Compnay; Advisory/Consultancy, Speaker Bureau/Expert testimony: Novartis; Advisory/Consultancy, Research grant/Funding (institution): Roche. J. Cortés: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Roche; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Celgene; Advisory/Consultancy: Cellestia; Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Advisory/Consultancy: Biothera Pharmaceutical; Advisory/Consultancy: Merus; Advisory/Consultancy: Seattle Genetics; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Daiichi Sankyo; Advisory/Consultancy: Erytech; Advisory/Consultancy: Athenex; Advisory/Consultancy: Polyphor; Honoraria (self), Advisory/Consultancy: Eli Lilly and Company; Advisory/Consultancy: Servier; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Merck Sharp&Dohme; Advisory/Consultancy: GSK; Advisory/Consultancy: Leuko; Advisory/Consultancy: Bioasis; Advisory/Consultancy: Clovis Oncology; Advisory/Consultancy: Boehringer Ingelheim; Honoraria (self), Travel/Accommodation/Expenses: Novartis; Honoraria (self), Research grant/Funding (institution), Travel/Accommodation/Expenses: Eisai; Honoraria (self), Research grant/Funding (institution), Travel/Accommodation/Expenses: Pfizer; Honoraria (self): Samsung Bioepis; Research grant/Funding (institution): Ariad Pharmaceuticals; Research grant/Funding (institution): Baxalta GMBH/Servier Affaires; Research grant/Funding (institution): Bayer Healthcare; Research grant/Funding (institution): F. Hoffman-La Roche; Research grant/Funding (institution): Guardanth Health; Research grant/Funding (institution): Piqur Therapeutics; Shareholder/Stockholder/Stock options: MedSIR; Research grant/Funding (institution): Puma C; Research grant/Funding (institution): Queen Mary University of London. P. Neven: Honoraria (self), Research grant/Funding (institution), Travel/Accommodation/Expenses: Eli Lilly and Company. F. Boyle: Honoraria (self), Advisory/Consultancy: Eli Lilly and Company; Honoraria (self), Advisory/Consultancy: Roche; Honoraria (self), Advisory/Consultancy: Pfizer; Honoraria (self), Advisory/Consultancy: Novartis. I. Smith: Full/Part-time employment, Former employee of Eli Lilly and Company: Eli Lilly and Compnay. D. Headley: Shareholder/Stockholder/Stock options, Full/Part-time employment: Eli Lilly and Company; Shareholder/Stockholder/Stock options: Novartis; Shareholder/Stockholder/Stock options: Takeda; Shareholder/Stockholder/Stock options: Varian Medical Systems; Shareholder/Stockholder/Stock options: Utah Medical Products; Shareholder/Stockholder/Stock options: Zoetis; Shareholder/Stockholder/Stock options: Bayer; Shareholder/Stockholder/Stock options: Merck; Shareholder/Stockholder/Stock options: Roche; Shareholder/Stockholder/Stock options: Evgen; Shareholder/Stockholder/Stock options: AstraZeneca; Shareholder/Stockholder/Stock options: Johnson & Johnson; Shareholder/Stockholder/Stock options: Pfizer; Shareholder/Stockholder/Stock options: Varex Imaging; Shareholder/Stockholder/Stock options: Zimmer BioMet; Shareholder/Stockholder/Stock options: Chugai Pharma. R. Wei: Shareholder/Stockholder/Stock options, Full/Part-time employment: Eli Lilly and Company. M. Frenzel: Shareholder/Stockholder/Stock options, Full/Part-time employment: Eli Lilly and Company. J. Cox: Shareholder/Stockholder/Stock options, Full/Part-time employment: Eli Lilly and Company. J. O'Shaughnessy: Advisory/Consultancy: AbbVie; Advisory/Consultancy: Agendia; Advisory/Consultancy: Amgen Biotechnology; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Britol-Myers Squibb; Advisory/Consultancy: Celgene; Advisory/Consultancy: Eisai; Advisory/Consultancy: Genentech; Advisory/Consultancy: Genomic Health; Advisory/Consultancy: GRAIL; Advisory/Consultancy: Immunomedics; Advisory/Consultancy: Heron Therapeutics; Advisory/Consultancy: Ipsen Biopharmaceuticals; Advisory/Consultancy: Jounce Therapeutics; Advisory/Consultancy: Eli Lilly and Company; Advisory/Consultancy: Merck; Advisory/Consultancy: Myriad; Advisory/Consultancy: Novartis; Advisory/Consultancy: Ondonate Therapeutics; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Puma Biotechnology; Advisory/Consultancy: Prime Oncology; Advisory/Consultancy: Roche; Advisory/Consultancy: Seattle Genetics; Advisory/Consultancy: Syndax Pharmaceuticals; Advisory/Consultancy: Takeda. P. Rastogi: Travel/Accommodation/Expenses: Eli Lilly and Company; Travel/Accommodation/Expenses: AstraZeneca; Travel/Accommodation/Expenses: Roche/Genentech. All other authors have declared no conflicts of interest.