A safety analysis of the MONARCH 2 and MONARCH 3 clinical trials suggests that abemaciclib may be generally well tolerated by patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2–) advanced breast cancer. Findings of the analysis were reported in the journal The Oncologist.

The analysis focused on safety outcomes in the randomized phase 3 MONARCH 2 (ClinicalTrials.gov Identifier: NCT02107703) and MONARCH 3 (ClinicalTrials.gov Identifier: NCT02246621) trials. The study investigators evaluated the incidence and management of clinically relevant adverse events (AEs). A total of 768 patients in this analysis received abemaciclib in addition to an endocrine therapy (ET) such as fulvestrant (MONARCH 2) or a nonsteroidal aromatase inhibitor (MONARCH 3). Both studies were placebo controlled.

Diarrhea was the most common AE reported among patients receiving abemaciclib, with grade 2 or higher diarrhea found in 42.8% of these patients. This was managed mostly by antidiarrheal medications, with dose omissions, dose reductions, or treatment discontinuation used in some cases. Grade 2 or higher diarrhea was more common in initial cycles than in later cycles.


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Grade 3 or higher neutropenia was found in 25.4% of patients on abemaciclib, while lower rates were reported for febrile neutropenia (<1%) and other grade 3 or higher hematologic AEs (<10%). Interstitial lung disease/pneumonitis occurred in a total of 26 patients. Of note, progression-free survival did not appear to be impaired by dose reductions or the presence of AEs such as diarrhea or neutropenia early on.

“In general, abemaciclib plus ET exhibits a generally tolerable safety profile, and side effects in MONARCH 2 and MONARCH 3 were predictable, manageable, and reversible upon treatment discontinuation,” wrote the study investigators in their report.

The investigators also noted that patients should be informed of the symptoms of interstitial lung disease/pneumonitis and that even in the context of dose reductions or AEs, patients experienced a progression-free survival benefit with abemaciclib.

Disclosures: Multiple authors declared affiliation with industry. Please refer to the original study for a full list of disclosures.

Reference

Rugo HS, Huober J, García-Sáenz JA, et al. Management of abemaciclib-associated adverse events in patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer: safety analysis of MONARCH 2 and MONARCH 3. Oncologist. Published online September 21, 2020. doi:10.1002/onco.13531