e-Poster Presentation Clinical Oncology Society of Australia Annual Scientific Meeting 2020

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 (#235)

Elgene Lim 1 , Frances Boyle 2 , Meena Okera 3 , Sherene Loi 4 , Sema S Goksu 5 , Gertjan van Hal 6 , Jonathon C Gable 6 , Gregory L Price 6 , Anwar Hossain 6 , Mary Gainford 6 , Meritxell B Ezquerra 7
  1. Garvan Institute of Medical Research and The Kinghorn Cancer Centre, Darlinghurst, NSW, Australia
  2. Oncology, Mater Hospital, North Sydney, NSW, Australia
  3. Oncology, Adelaide Cancer Centre, Kurralta Park, South Australia, Australia
  4. Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia
  5. Medical Faculty, Akdeniz University , Antalya, Turkey
  6. Eli Lilly and Company, Indianapolis, Indiana, USA
  7. Vall d’Hebron Institute of Oncology , Hospital Universitari Vall d'Hebron , Barcelona, Spain

Aims: Study I3Y-MC-JPCP (multicenter, randomized, open-label phase 2) evaluated food’s impact on incidence of Grade3 or prolonged Grade2 diarrhea in HR+, HER2− metastatic breast cancer (mBC) patients receiving abemaciclib monotherapy 200mg orally BID during first 3 cycles of treatment.

Methods: Patients with HR+, HER2− mBC and ECOG performance status≤1 who progressed after prior anti-estrogen therapy for mBC and received prior treatment with ≥1 chemotherapy regimen for mBC (CDK4/6i-naive) were randomly assigned 1:1:1 to receive abemaciclib with a meal, in a modified fasted condition (defined as ≥1h before or ≥2h after a meal), or without regard to food. Primary study endpoints: incidence of ≥Grade3 diarrhea; incidence of Grade2 diarrhea lasting>7 days; dose reductions, dose interruptions, treatment discontinuations due to diarrhea; use of antidiarrheal agents. Secondary endpoints included overall safety and pharmacokinetic analysis. A patient-held electronic diary recorded daily information on number of stools, diarrhea, loperamide use, timing of abemaciclib intake relative to meals. Compliance with diary completion was centrally monitored.

Results: Of 72 patients randomized in five countries from December2018-April2019, 71 (median age 56.0 years) were treated with abemaciclib in one of three study arms: with a meal (Arm1, n=24), modified fasted condition (Arm2, n=23) and without regard to food (Arm3, n=24). Primary endpoints during the first three treatment cycles for Arm1/Arm2/Arm3: ≥1 Grade2 diarrhea lasting>7 days(%)=8.3/17.4/20.8; ≥1 Grade3 diarrhea(%)=4.2(duration:1day)/0/0; ≥1 Dose reduction and interruption due to diarrhea(%)=16.7,16.7/8.7,4.3/12.5,8.3; Treatment discontinued due to diarrhea(%)=0/0/0; Loperamide use(%)=95.8/91.3/95.8.

Most frequently reported Grade3/4 TEAEs related to treatment: neutropenia(28.2%), leukopenia(11.3%), thrombocytopenia(7.0%), fatigue(5.6%), nausea(5.6%), lymphopenia(5.6%).

Conclusions: Global compliance with e-diary completion and meal condition:>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.

Reused with permission 2019-SABCS®.