Safety in Japanese Advanced Breast Cancer Patients Who Received Abemaciclib in MONARCH 2 and MONARCH 3: Assessment of Treatment-Emergent Neutropenia, Diarrhea, and Increased Alanine Aminotransferase and Aspartate Aminotransferase Levels

Abstract

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 [phone], Fax [phone], Email [email protected]: 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 3– 4, 35.6%), increased alanine aminotransferase (ALT; any grade, 39.6%; Grade 3– 4, 14.9%), and increased aspartate aminotransferase (AST; any grade, 37.6%; Grade 3– 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

Keywords

• abemaciclib
• breast cancer
• cyclin-dependent kinase 4/6
• fulvestrant
• nonsteroidal aromatase inhibitor