Abstract 277P
Background
Abemaciclib-induced diarrhea (AID) occurs about 80-90% of patients, resulting in the impairment of QOL and compliance. Previous reports showed that over 40% patients had constipation due to prophylactic use of loperamide. We hypothesized that bifidobacterial and trimebutine maleate decrease the frequency of AID without increasing constipation.
Methods
Women with estrogen receptor-positive, HER2-negative inoperable and/or recurrent breast cancers were enrolled and randomized into bifidobacterial (arm A) or bifidobacterial and trimebutine maleate (TM; arm B). Both arms received hormone therapies and abemaciclib over 28 days, and simultaneously were given at least more than 60mg/day bifidobacterial. Once patients experienced type-6 or -7 diarrhea on the Bristol scale, salvage use of loperamide was required. In addition to loperamide, patients in arm B were administered TM. Information on diarrhea and other side effects were reported by each patient with a medication diary and confirmed by the physician every two weeks. The primary endpoint is percentage of patients who experienced onset of grade 2 or higher diarrhea, and the statistical threshold was set at 40% based on historical data. The secondary endpoints are safety, frequency and duration of all-grade diarrhea, frequency of emesis and constipation, use of loperamide, and QOL/PRO in the 28-day study duration.
Results
Fifty three patients were enrolled and 51 patients completed the study treatments. Two patients terminated due to grade 4 hepatic dysfunction and exacerbation of comorbidities. Grade 2 diarrhea occurred in 54.2 and 50.0% of arm A and B. Only one patient occurred grade 3 diarrhea in each arm. The median duration of grade 2 or higher diarrhea was one day. Constipation of grade 2 or higher was observed in 4 and 3.6% in arm A and B.
Conclusions
Although the incidence of diarrhea did not improve in both arms compared to historical data, bifidobacterial with or without TM shortened the duration of AID and prevented grade 3 or higher diarrhea, while the rate of constipation unchanged. As a result, the incidences of drug suspension/reduction were decreased.
Clinical trial identification
WJOG11318B.
Editorial acknowledgement
Legal entity responsible for the study
West Japan Oncology Group (WJOG)
Funding
Lilly.
Disclosure
H. Masuda: Financial Interests, Personal, Invited Speaker: Lilly; Financial Interests, Institutional, Research Grant: Lilly. K. Matsumoto: Financial Interests, Personal, Other, honoraria: Lilly; Financial Interests, Institutional, Research Grant: Lilly. A. Shimomura: Financial Interests, Personal, Invited Speaker: Lilly. Y. Miyoshi: Financial Interests, Personal, Invited Speaker: Lilly; Financial Interests, Institutional, Funding: Lilly; Financial Interests, Institutional, Research Grant: Lilly; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Institutional, Research Grant: Pfizer; Financial Interests, Personal, Invited Speaker: AstraZeneca. M. Takahashi: Financial Interests, Personal, Other, honoraria: Lilly; Financial Interests, Personal, Other, honoraria: AstraZeneca; Financial Interests, Personal, Other, honoraria: Pfizer; Financial Interests, Personal, Other, honoraria: Eisai. Y. Sagara, N. Niikura, K. Yoshimura, T. Takano: Financial Interests, Personal, Other, honoraria: Lilly. J. Tsurutani: Financial Interests, Personal, Advisory Role: Lilly; Financial Interests, Personal, Other: Lilly. All other authors have declared no conflicts of interest.