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Breast cancer, metastatic

774 - A phase 1b study of abemaciclib, an inhibitor of CDK4 and CDK6, in combination with endocrine and HER2-targeted therapies for patients with metastatic breast cancer


09 Oct 2016


Breast cancer, metastatic


Muralidhar Beeram


Annals of Oncology (2016) 27 (6): 1-36. 10.1093/annonc/mdw435


M. Beeram1, S.M. Tolaney2, J.T. Beck3, M.N. Dickler4, A.K. Conlin5, C. Dees6, T.L. Helsten7, P.R. Conkling8, W.J. Edenfield9, D.A. Richards10, S.R.P. Kambhampati11, T.M. Costigan11, E. Chan12, S. Pant13, K. Kalinsky14, C.H. Becerra15, H.A. Burris16, B.N. Rexer17, S.L. Puhalla18, M.P. Goetz19

Author affiliations

  • 1 The Start Center For Cancer Care, South Texas Accelerated Research Therapeutics (START), 78229 - San Antonio/US
  • 2 Breast Oncology Center, Dana-Farber Cancer Institute, Boston/US
  • 3 Hematology, Highlands Oncology Group, Rogers/US
  • 4 Oncology, Memorial Sloan-Kettering Cancer Center, New York/US
  • 5 Medical Oncology, Providence Cancer Center, 97213 - Portland/US
  • 6 Oncology, Lineberger Comprehensive Cancer Center University of North Carolina, Chapel Hill/US
  • 7 Medicine, University of California San Diego, La Jolla/US
  • 8 Virginia Oncology Associates, US Oncology Research, Norfolk/US
  • 9 Clinical Research Unit, Institute for Translational Oncology Research, Greenville Hospital System,, Greenville/US
  • 10 Texas Oncology, US Oncology Research, Tyler/US
  • 11 Oncology, Eli Lilly and Company, Indianapolis/US
  • 12 Oncology, Eli Lilly and Company, 46285 - Indianapolis/US
  • 13 Cancer Therapeutics, MD Anderson Cancer Center, Houston/US
  • 14 Medical Center, Columbia University, New York/US
  • 15 Baylor University Medical Center, US Oncology Research, Texas Oncology, Dallas/US
  • 16 Dept. Drug Development, Sarah Cannon Research Institute, 37203 - Nashville/US
  • 17 Medicine, Vanderbilt University, Nashville/US
  • 18 Medicine, Magee-Womens Hospital of UPMC, Pittsburgh/US
  • 19 Oncology, Mayo Clinic, Rochester/US


Abstract 774


Abemaciclib is a selective inhibitor of CDK4 and CDK6 with a safety profile that enables continuous dosing to maintain target coverage. Abemaciclib has demonstrated antitumour activity for previously treated hormone receptor (HR)+ metastatic breast cancer (MBC) as a single agent and with fulvestrant (Patnaik et al, 2016). The objective of this study was to evaluate abemaciclib with either endocrine-based therapies or trastuzumab (T).


Eligibility criteria allowed nonmeasureable disease and ongoing treatment with combination drug(s) at study entry. Patients (pts) with HR+ HER2- MBC received abemaciclib orally every 12 hours plus the following therapies daily until progression: anastrozole (n = 16), letrozole (n = 20), tamoxifen (n = 16), exemestane (n = 15), or exemestane + everolimus (n = 19). Patients receiving exemestane-based therapy must have received 31 nonsteroidal aromatase inhibitor for metastatic disease. Patients with HER2+ MBC (either HR+ or HR-) received abemaciclib plus T every 21 days (n = 24). Adverse events were graded by NCI CTCAE v4.0 and tumour response was assessed by RECIST 1.1.


For all combinations, the most common treatment-emergent adverse events (TEAEs) included fatigue and effects on the gastrointestinal and hematologic systems. For the combination with exemestane + everolimus, the most common TEAEs also included stomatitis, leukopenia, thrombocytopenia, and rash. For each combination, objective response and clinical benefit rates are shown in Table 1. Objective responses and durable disease control were observed for all combinations among HR+ tumours including those with HER2 amplification.

Drug(s) combined with Abemaciclib # Patients Evaluable for Response Objective Response Ratea n (%) Clinical Benefit Rateb n (%)
Anastrozole 15 3 (20) 13 (87)
Letrozole 14 2 (14) 8 (57)
Tamoxifen 15 3 (20) 12 (80)
Exemestane 13 6 (46) 9 (69)
Exemestane + Everolimus 15 5 (33) 11 (73)
Trastuzumab / HR + 12 2 (17) 5 (42)

acomplete response + partial response

bcomplete response + partial response + stable disease ≥6 months


Abemaciclib shows acceptable safety with either endocrine-based therapies or trastuzumab. For women with HR+ MBC, including some HER2+ tumours, these combinations demonstrate clinical activity with objective responses and durable disease control.

Clinical trial identification


Legal entity responsible for the study

Eli Lilly and Company


Eli Lilly and Company


M. Beeram: I have no direct financial interest in products or processes involved in this research. My parent company, START, San Antonio is reimbursed by Eli-Lilly for the conduct of this study which qualifies as corporate-sponsored research. S.M. Tolaney: Research funding from: Lilly, Exelixis, Genentech, Novartis, Merck, Pfizer M.N. Dickler: Steering committee with Lilly Consulting with Roche/Genentech, Novartis and Pfizer Research support; Lilly, Roche/Genentech, Novartis and Astra Zeneca. C. Dees: Research funding (Institution) Novartis, Agensys, Aveo, GSK, Genetech, Millenium, advisory role Novartis. P.R. Conkling: My only source of research funding is USOncology Research. I have no other financial interests to declare. W.J. Edenfield: Speakers Bureau: Astellas/Medivation and Novartis No other conflicts to report. D.A. Richards: Honoraria, and advisory role Novartis. S.R.P. Kambhampati, T.M. Costigan, E. Chan: I am an employee of Eli Lilly and Company with stock ownership. K. Kalinsky: My spouse works for Novartis - however, my spouse's research is completely unrelated to this project. Also, I have received honoraria from Pfizer, Immunomedics, AstraZeneca, and Amgen on projects completed unrelated to this. C.H. Becerra: Research funding (Institution) and Speakers' Bureau Eli Lilly and company S.L. Puhalla: Consulting- Celldex, MedImmune, Pfizer, Abbvie Research Funding- Novartis, Abbvie, Lilly, Pfizer, Incyte, Covance-Bayer M.P. Goetz: Consultant for Lilly, Pfizer, AbbVie and bioTheranostics. All monies received from consulting are paid to Mayo Foundation. All other authors have declared no conflicts of interest.

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