In the MONARCH plus study, the majority of abemaciclib-associated diarrhea events were low grade in severity and well managed by antidiarrheal medications, dose omissions, and/or dose reductions.
At the interim analysis of the MONARCH plus study, abemaciclib, a CDK4/6 inhibitor administered in combination with nonsteroidal aromatase inhibitors or with fulvestrant, compared with placebo demonstrated efficacy and an acceptable safety profile in postmenopausal women with hormone receptor–positive, HER2-negative locoregionally recurrent or metastatic breast cancer.
Diarrhea was found to be one of the most common treatment-emergent adverse events, typically of low grade and early onset. In this study, Zefei Jiang, MD, Director, Breast Cancer, The Fifth Medical Center of PLA General Hospital, Beijing, China, and colleagues examined abemaciclib-associated diarrhea and reviewed its management in the MONARCH plus trial.
Two cohorts of patients were included in the MONARCH plus study. The first cohort included patients with initial treatment of endocrine therapy who received abemaciclib or placebo plus nonsteroidal aromatase inhibitor (anastrozole or letrozole). The second cohort included patients who progressed on previous endocrine therapy, receiving abemaciclib or placebo plus fulvestrant.
The relative dose intensity was defined as the percentage of actual dose received relative to the planned dose. Diarrhea severity was graded according to Common Terminology Criteria for Adverse Events version 4.0 as reported by investigators.
Additional analysis included time to onset of diarrhea, duration, supportive medication, and dose modifications. For the study, progression-free survival (PFS) was defined as time from randomization to death or progression (as per Response Evaluation Criteria in Solid Tumors version v1.1).
The median relative dose intensity of abemaciclib in the abemaciclib plus nonsteroidal aromatase inhibitors arm and abemaciclib plus fulvestrant arm were similar at 96.77% and 96.30%, respectively.
In the abemaciclib plus nonsteroidal aromatase inhibitors arm and abemaciclib plus fulvestrant arm, the median time to onset of first reported diarrhea was 7 days and 6 days, respectively, and the majority of diarrhea events occurred early (66.3% and 71.2% of patients reported diarrhea in cycle 1, respectively).
Low grade 3 diarrhea was reported by 3.9% of patients in the abemaciclib plus nonsteroidal aromatase inhibitors arm and 1.9% in the abemaciclib plus fulvestrant arm, and grade ≥3 diarrhea for a median duration of 2.5 days and 3.5 days, respectively. No grade 4 diarrhea was reported in either arm.
With dose adjustments and/or supportive medication, diarrhea was generally managed. Dose reductions were present in 2.0% of the abemaciclib combined with nonsteroidal aromatase inhibitors arm and 2.9% of the abemaciclib plus fulvestrant arm, and antidiarrheal therapy was prescribed in 30.2% and 32.7% of patients, respectively.
Most diarrhea events were resolved as data cutoff approached, and by cycle 2 the incidence dropped below 10% (grade 2) and 1% (grade 3) in both arms and stayed at a sustained, low incidence over time. Patients treated with the abemaciclib combination who reported diarrhea within the first week (abemaciclib plus nonsteroidal aromatase inhibitors: hazard ratio [HR], 0.289; 95% confidence interval [CI], 0.166-0.502; abemaciclib plus fulvestrant: HR, 0.371; 95% CI, 0.213-0.647) had significant improvement in PFS, when compared with the placebo arm.
The bulk of diarrhea events were well managed by antidiarrheal medications, dose omissions, and/or dose reductions in MONARCH plus patients, and the events were low grade in severity.
Source: Jiang Z, Hu X, Zhang Q, et al. Management of abemaciclib associated diarrhea in patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer: analysis of the MONARCH plus study. Presented at: 2020 San Antonio Breast Cancer Symposium, December 8-11, 2020. Abstract PS13-25.