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Norikazu Masuda,1 Yucherng Chen,2 Tsutomu Kawaguchi,3 Koji Dozono,4 Masakazu Toi5 1Department of Breast and Endocrine Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan; 2Safety Science, Quality and Patient Safety, Eli Lilly Japan K.K., Kobe, Japan; 3Medicines Development Unit, Eli Lilly Japan K.K., Kobe, Japan; 4Global Statistical Science Japan, Eli Lilly Japan K.K., Kobe, Japan; 5Breast Cancer Unit, Kyoto University Hospital and Breast Surgery, Graduate School of Medicine, Kyoto University, Kyoto, JapanCorrespondence: Masakazu Toi, Breast Cancer Unit, Kyoto University Hospital and Breast Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan, Tel +81-75-751-3660, Fax +81-75-751-3616, Email toi@kuhp.kyoto-u.ac.jpPurpose: Our objective was to gain a better understanding of the safety of abemaciclib in Japanese patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer.Patients and Methods: Treatment-emergent adverse events (TEAEs) were assessed in pooled Japanese subpopulation data from two phase 3 studies assessing abemaciclib/placebo in combination with fulvestrant (MONARCH 2; M2) or non-steroidal aromatase inhibitors (MONARCH 3; M3). For common, clinically relevant TEAEs, event characteristics and management were summarized by study.Results: In the Japanese safety subpopulation (abemaciclib: N=101; placebo: N=46), all patients experienced ⥠1 TEAE (Grade ⥠3: abemaciclib, 71.3%; placebo, 23.9%; no Grade 5). Clinically relevant TEAEs that were more frequent in abemaciclib-treated Japanese patients compared to the overall safety populations included diarrhea (any grade, 95.0%; Grade ⥠3, 12.9%), neutropenia (any grade, 75.2%; Grade 3â 4, 35.6%), increased alanine aminotransferase (ALT; any grade, 39.6%; Grade 3â 4, 14.9%), and increased aspartate aminotransferase (AST; any grade, 37.6%; Grade 3â 4, 8.9%). Diarrhea was Grade ⤠3 and successfully managed with medications (⥠87%) and dose reductions (⤠25%) and/or omissions (⤠23.3%). Most Grade ⥠2 diarrhea occurred in the first treatment cycle, declining thereafter. Neutropenia, the most common Grade ⥠3 TEAE in abemaciclib-treated Japanese patients, was generally manageable with dose omissions (M2: 42.0%; M3: 23.1%) and/or reductions (M2: 16%; M3: 15.4%). Neutrophil counts plateaued after Cycle 2, recovering to pretreatment levels after discontinuation of abemaciclib. Hepatic events were managed with medication (⤠21%) and dose adjustments (⤠33.3%), with most Grade ⥠2 events occurring in early treatment cycles. Discontinuation of any study treatment in Japanese patients occurred more frequently due to increased ALT/AST (M2: 9.1%/10.5%; M3: 16.7%/10.5%) compared with diarrhea (M2: 0%; M3: 2.8%) or neutropenia (M2: 0%; M3: 3.8%).Conclusion: Abemaciclib was well tolerated in Japanese patients in MONARCH 2 and MONARCH 3, with common, clinically relevant TEAEs manageable with appropriate interventions.Graphical Abstract: Keywords: abemaciclib, breast cancer, cyclin-dependent kinase 4/6, fulvestrant, nonsteroidal aromatase inhibitor |
