Abstract P5-14-05: The impact of food on tolerability of abemaciclib in patients with previously treated hormone receptor-positive, HER2-negative, metastatic breast cancer: An open-label, randomized phase 2 study
Authors: Lim Elgene , Boyle Frances , Okera Meena , Loi Sherene , Goksu Sema Sezgin , van Hal Gertjan , Hartman Daisy G , Gable Jonathon Colby , Price Gregory L , Hossain Anwar , Gainford M C , Ezquerra Meritxell Bellet 
Published: March 2020

Abstract
Background: Abemaciclib is an orally administered inhibitor of cyclin-dependent kinase (CDK) 4/6, dosed twice daily (BID) on a continuous schedule. Diarrhea is a frequently associated adverse event. It is predictable and manageable with antidiarrheal medication, typically occurs within the first month of therapy, and decreases over the duration of treatment. In the MONARCH 1, 2, and 3 studies, Grade 3 diarrhea was experienced by 9% to 20% of patients (pts) receiving abemaciclib. Study design/Objectives: Study I3Y-MC-JPCP (ClinicalTrials.gov, NCT03703466) was a multicenter, randomized, open-label phase 2 study designed to evaluate the impact of food on the incidence of Grade 3 or prolonged Grade 2 diarrhea in HR+, HER2− metastatic breast cancer (mBC) pts receiving abemaciclib monotherapy 200 mg orally BID during the first 3 cycles of study treatment. Methods: Pts with HR+, HER2− mBC and ECOG performance status ≤1 who had progressed after prior anti-estrogen therapy for mBC and received prior treatment with ≥1 chemotherapy regimen for mBC, but were CDK4/6i naive, were randomly assigned 1:1:1 to receive abemaciclib with a meal, in a modified fasted condition (defined as ≥1 h before or ≥2 h after a meal), or without regard to food. Primary study endpoints were the incidence of ≥Grade 3 diarrhea; incidence of Grade 2 diarrhea lasting &gt;7 days; dose reductions, dose interruptions, and treatment discontinuations due to diarrhea; and use of antidiarrheal agents. Secondary endpoints included overall safety and pharmacokinetic analysis. A pt-held electronic diary was used to record daily information on number of stools, diarrhea, loperamide use, and timing of abemaciclib intake relative to meals. Compliance with diary completion was centrally monitored. Multicenter training and implementation of e-diaries used a variety of paper and electronic resources tailored to end user (research staff, site staff, patient). Physicians had real-time access to data enabling accurate assessment of diarrhea. Results: This study randomized 72 pts in five countries from December 2018 to April 2019; 71 pts (median age 56.0 y) were treated with abemaciclib in one of three study arms: with a meal (Arm 1, n=24), modified fasted condition (Arm 2, n=23) and without regard to food (Arm 3, n=24). Mean compliance for e-diary completion was 95.7% for the overall population. Mean compliance with meal conditions was 99.5% in Arm 1 and 95.2% in Arm 2 (not applicable for Arm 3). In Arms 1, 2 and 3, 83.3%, 78.3% and 91.7% of pts received ≥3 cycles, respectively. Primary endpoints during the first three treatment cycles are summarized (Table).
Table 1Arm 1 (n=24)Arm 2 (n=23)Arm 3 (n=24)Overall (n=71)≥1 Grade 2 diarrhea lasting &gt;7 days, %8.317.420.815.5≥1 Grade 3 diarrhea, %4.2*001.4≥1 Grade 4 diarrhea, %0000≥1 Dose reduction due to diarrhea, %16.78.712.512.7≥1 Dose interruption due to diarrhea, %16.74.38.39.9Treatment discontinued due to diarrhea, %0000Loperamide use, %95.891.395.894.4* Duration of Grade 3 diarrhea was 1 day.
This study was descriptive and not powered to analyze differences between study arms. Overall, the most frequently reported Grade 3/4 treatment-emergent adverse events related to treatment were neutropenia (28.2%), leukopenia (11.3%), thrombocytopenia (7.0%), fatigue (5.6%), nausea (5.6%) and lymphopenia (5.6%). Details on patient-reported diarrhea incidence and management, and PK analyses will be presented at conference. Conclusions: Global compliance with e-diary completion and meal condition was &gt;95%. Diarrhea at high grade occurred at much lower incidence than previously reported (1.4% overall) and was of short duration (1 day). Diarrhea was predominantly low grade and managed with loperamide and dose modifications in all meal cohorts.
Citation Format: Elgene Lim, Frances Boyle, Meena Okera, Sherene Loi, Sema Sezgin Goksu, Gertjan van Hal, Daisy G Hartman, Jonathon Colby Gable, Gregory L Price, Anwar Hossain, M C Gainford, Meritxell Bellet Ezquerra. The impact of food on tolerability of abemaciclib in patients with previously treated hormone receptor-positive, HER2-negative, metastatic breast cancer: An open-label, randomized phase 2 study [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-14-05.