Abstract CT092: A phase II study of neoadjuvant abemaciclib (LY2835219) in postmenopausal women with hormone receptor positive (HR+), human epidermal growth factor receptor 2 negative (HER2-) breast cancer (neoMONARCH)
Authors: Hurvitz Sara A. , Schilder Jeanne Marie , Frenzel Martin , Martín Miguel 
Published: July 2016

Purpose: Abemaciclib (LY2835219) is a potent, selective small molecule inhibitor of cyclin dependent kinase (CDK)4 and CDK6, which has been shown to inhibit cell cycle progression by preventing the phosphorylation and functional inactivation of the Rb tumor-suppressor protein. Cell cycle dysfunction due to abnormalities in the CDK4 and CDK6 pathway occurs in breast cancer. Abemaciclib demonstrated single-agent activity in heavily pretreated women with HR+ metastatic breast cancer (Study I3Y-MC-JPBA), and has an acceptable safety profile as a single agent and when combined with aromatase inhibitors. neoMONARCH (NCT02441946) is a randomized, open-label phase II study comparing the biologic activity of abemaciclib plus anastrozole, abemaciclib monotherapy, and anastrozole monotherapy in postmenopausal women with early-stage HR+, HER2- breast cancer by assessing percentage change from baseline in Ki67 expression after 2 weeks of therapy. Secondary objectives are to evaluate response rates, safety, quality of life, and pharmacokinetics of abemaciclib and anastrozole with up to 22 additional weeks of neoadjuvant therapy.

Methods: Approximately 220 patients with HR+, HER2- breast cancer who have received no prior treatment for newly diagnosed invasive breast cancer will be randomized 1:1:1 (Arm A [abemaciclib 150 mg orally q12hrs plus anastrozole 1 mg orally q24hrs], Arm B [abemaciclib 150 mg orally q12hrs], Arm C [anastrozole 1 mg orally q24hrs]) for 2 weeks, with stratification based on progesterone receptor status and tumor size (&lt;2 versus ?2 cm and &lt;5 versus ?5 cm). During the subsequent 14 weeks, all patients will receive abemaciclib 150 mg orally q12hrs plus anastrozole 1 mg orally q24hrs. Patients experiencing benefit, but not a complete response, will have the option to continue combination therapy for an additional 2 cycles (up to 8 additional weeks) at the discretion of the investigators. All patients will receive prophylactic loperamide during abemaciclib therapy. Eligible patients include postmenopausal women with HR+, HER2- clinical Stage I breast tumor ?1 cm in diameter, Stage II, Stage IIIA, or IIIB breast cancer. Patients are required to have ?1 measurable lesion, adequate organ function, and an ECOG performance status of ?1. Patients’ primary breast cancer must be suitable for baseline core biopsy.

Statistical methods: The study has &gt;80% power to detect a superior effect of the combination therapy or of abemaciclib alone over anastrozole alone in reducing Ki67 expression at a 1-sided alpha level of 0.1, assuming a geometric mean change in Ki67 expression of -82% for anastrozole alone and -91% for combination therapy or abemaciclib alone.

Present accrual: 73 patients.

Citation Format: Sara A. Hurvitz, Jeanne Marie Schilder, Martin Frenzel, Miguel Martín. A phase II study of neoadjuvant abemaciclib (LY2835219) in postmenopausal women with hormone receptor positive (HR+), human epidermal growth factor receptor 2 negative (HER2-) breast cancer (neoMONARCH). [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr CT092.