Abstract PD5-01: Final results of NeoMONARCH: A phase 2 neoadjuvant study of abemaciclib in postmenopausal women with hormone receptor positive (HR+), HER2 negative breast cancer (BC)
Authors: Martin M , Hurvitz SA , Chan D , Fernandez-Abad M , Petru E , Rostorfer R , Guarneri V , Huang C-S , Press MF , Costigan TM , Caldwell CW , Wijayawardana S , Turner PK , Barriga S , Slamon DJ 
Published: February 2018

Abstract
Background: Abemaciclib is a selective oral inhibitor of CDK4 and CDK6. Dosed on a continuous schedule, abemaciclib showed evidence of antitumor clinical activity in patients (pts) with metastatic BC in monotherapy or in combination with non-steroidal aromatase inhibitor (NSAI) or fulvestrant. NeoMONARCH (NCT02441946) is a Phase 2 trial in women with stage I-IIIB, HR+/HER2- BC evaluating neoadjuvant treatment with abemaciclib + anastrozole, ANZ. As previously reported, NeoMONARCH met its primary endpoint showing abemaciclib, alone or in combination with ANZ, significantly reduced Ki67 expression compared to ANZ alone after 2 weeks (wks) of treatment. Final results are presented here.
Methods: 223 pts were randomized (1:1:1) and treated for 2 wks with abemaciclib (150 mg PO Q12H) + ANZ (1 mg PO QD), abemaciclib alone, or ANZ alone. Then, all pts were treated for 14 wks with the combination. Pts were treated with loperamide (2 mg PO Q12H) for 4 wks while receiving abemaciclib. Tumor biopsy was collected at baseline, Wk 2 and Wk 16. Blood samples were collected through Cycle 5 to measure abemaciclib and ANZ concentrations. Primary objective was Ki67 change from baseline to Wk 2. Secondary objectives evaluated after Wk 16 of treatment, were radiologic, pathological and clinical responses, safety, and pharmacokinetics (PK). Exploratory objectives included the mutational analysis of PIK3CA and ESR1 at baseline.
Results: Table 1 shows subgroup analyses of percent change in Ki67 from baseline to Wk 2 by disease stage, baseline lymph node (LN) involvement, tumor grade, and tumor size in Ki67 evaluable (KE) population (baseline Ki67 ≥ 5%) comparing combination to ANZ alone. Data for abemaciclib arm will be shown at the meeting. 185 pts completed treatment. At the end of treatment, response rates were radiologic 46.4% (all pts), and caliper 53.6% (all pts), and pCR 3.7% (pts who completed BC surgery assessment). Ki67 end of treatment analysis in 138 pts will be presented. The most common adverse events, all pts, were diarrhea (61.4%; G3: 4.9%), constipation (43.5%; G3: 1.8%), and nausea (41.7%; G3: 2.2%). Treatment discontinuation due to AEs was low (7.6%). Results of PIK3CA and ESR1 mutational analysis, and PK will be presented.
Subgroup analyses at Wk 2 of KE population CombinationANZSubgroup treatment comparaison Pts, nGM % ChangePts, nGM % ChangeGMR (95% CI)PKE population59-92.8656-62.780.19 (0.13, 0.28)&lt;0.001Disease Stage I/II51-92.5646-65.840.22 (0.14, 0.34)&lt;0.001III7-95.288-54.910.10 (0.04, 0.27)&lt;0.001Baseline LN Involvement No29-93.1826-62.210.18 (0.11, 0.31)&lt;0.001Yes29-92.7528-69.020.23 (0.13, 0.42)&lt;0.001Tumor Grade 1 or 233-92.8837-69.610.23 (0.15, 0.36)&lt;0.001316-92.7910-59.680.18 (0.05, 0.60)0.011Tumor Size &lt; 2 cm9-93.258-65.460.20 (0.08, 0.35)0.004≥ 2 cm and &lt; 5 cm39-91.2229-62.160.23 (0.14, 0.40)&lt;0.001≥ 5 cm11-94.2419-59.730.14 (0.07, 0.28)&lt;0.001Abbreviations: GM, geometric mean; GMR, geometric mean ratio
Conclusions: Abemaciclib + ANZ is an effective treatment with manageable toxicities in pts with HR+/HER2- early BC. Abemaciclib-driven change in Ki67 was not associated with disease stage, baseline LN involvement, tumor grade, or tumor size.
Citation Format: Martin M, Hurvitz SA, Chan D, Fernandez-Abad M, Petru E, Rostorfer R, Guarneri V, Huang C-S, Press MF, Costigan TM, Caldwell CW, Wijayawardana S, Turner PK, Barriga S, Slamon DJ. Final results of NeoMONARCH: A phase 2 neoadjuvant study of abemaciclib in postmenopausal women with hormone receptor positive (HR+), HER2 negative breast cancer (BC) [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr PD5-01.