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®.