On February 26th, 2018, the FDA expanded approval of abemaciclib (VERZENIO™), manufactured by
Eli Lilly Inc., for the frontline treatment of hormone receptor (HR)-positive, human epidermal
growth factor receptor 2 (HER2)-negative advanced breast cancer (BC) in combination with an
aromatase inhibitor (AI) [1]. It was originally approved in September of 2017 for patients with
HR-positive, HER2-negative advanced BC who had previously received endocrine therapy [2].
Abemaciclib is a small molecule inhibitor of cyclin-dependent kinases (CDK) 4 and 6 which are
involved in cell cycle progression and the prevention of cellular senescence [3]. CDK4 and CDK6
overactivity has been implicated in several malignancies including non–small cell lung cancer
(NSCLC), melanoma, glioblastoma, mantle cell lymphoma, and BC [3].

The expanded approval was based on the results of a randomized phase 3 study, MONARCH 3,
which assessed the safety and efficacy of abemaciclib in combination with an AI versus an AI
alone for the treatment of HR-positive, HER2-negative advanced BC (NCT02246621) [6].
Patients in the abemaciclib arm experienced a prolonged median progression free survival, not
reached vs. 14.7 months and a higher objective response rate in patients with measurable
disease, 59% vs. 44% [7]. In general, the combination was found to be well tolerated with the
most common adverse event reported being diarrhea which was experienced in 81.3% of
patients (44.6% grade 1). Two other CDK4/6 inhibitors, ribociclib (Kisqali®) and palbociclib
(Ibrance®), have previously been approved for the frontline treatment of patients with HR-
positive, HER2-negative advanced BC, thus it may be difficult for oncologists to determine
which CDK4/6 inhibitor is appropriate for their patients [4, 5].

–Zachary Moore, on behalf of the Medical Content Team

  1.  VERZENIO™ (abemaciclib) tablets, for oral use. Drugs@FDA: FDA Approved Drug Products
    February 26, 2018 [cited 2018 April 13]; Available from:
    https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/208855s000lbl.pdf.
  2.  VERZENIO™ (abemaciclib) tablets, for oral use Drugs@FDA: FDA Approved Drug Products
    09/28/2017 [cited 2018 April 13]; Available from:
    https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/208716Orig1s000lbl.pdf.
  3. Gelbert, L.M., et al., Preclinical characterization of the CDK4/6 inhibitor LY2835219: in-vivo cell
    cycle-dependent/independent anti-tumor activities alone/in combination with gemcitabine.
    Invest New Drugs, 2014. 32(5): p. 825-37.
  4. KISQALI® (ribociclib) tablets, for oral use Drugs@FDA: FDA Approved Drug Products 03/13/2017
    [cited 2018 April 13]; Available from:
    https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209092s000lbl.pdf.
  5. IBRANCE® (palbociclib) capsules, for oral use Drugs@FDA: FDA Approved Drug Products
    02/06/2018 [cited 2018 April 13]; Available from:
    https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/207103s007lbl.pdf.
  6. A Study of Nonsteroidal Aromatase Inhibitors Plus Abemaciclib (LY2835219) in Postmenopausal
    Women With Breast Cancer (MONARCH 3). ClinicalTrials.gov March 23, 2018 [cited 2018 April
    13]; Available from: https://clinicaltrials.gov/ct2/show/NCT02246621.
  7.  Goetz, M.P., et al., MONARCH 3: Abemaciclib As Initial Therapy for Advanced Breast Cancer. J
    Clin Oncol, 2017. 35(32): p. 3638-3646.
Zachary Moore

Author Zachary Moore

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