Medical Oncology Unit, La Maddalena Clinic for Cancer, and Oncology Section, Department "Promise" of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, University of Palermo, Palermo, Italy;
Department of Clinical and Experimental Medicine, University of Catania, and Center of Experimental Oncology and Hematology AOU, Policlinico "G. Rodolico - San Marco", Catania, Italy.
Anticancer Res. 2023 Mar;43(3):1291-1299. doi: 10.21873/anticanres.16276.
BACKGROUND/AIM: Abemaciclib is a cyclin-dependent kinase 4/6 inhibitor approved in combination with endocrine therapy for treating hormone receptor-positive and human epidermal growth factor receptor 2-negative early and advanced breast cancer patients. The safety profile of abemaciclib is characterized by frequent gastrointestinal toxicity, especially diarrhea. Therefore, we performed an exploratory analysis of clinical factors that may be potentially associated with diarrhea in patients treated with abemaciclib plus endocrine therapy.
Factors potentially predisposing to diarrhea were selected, such as age ≥70 years, concomitant medications and diseases, diet, and use of laxatives. These variables were correlated with the onset of grade 2/3 diarrhea in a cohort of patients treated with abemaciclib from advanced breast cancer. Univariate and multivariate analysis was performed. Sensitivity and specificity were tested using the ROC curve.
Eighty women with advanced breast cancer were included in the study. The univariate analysis found a statistically significant correlation between grade 2/3 diarrhea and age ≥70 years, polypharmacy, and concomitant gastrointestinal diseases (p<0.05). In the multivariate analysis, the number of risk factors significantly correlated with the outcome of interest (p<0.0001). ROC analysis showed our model's 82% sensitivity and 75% specificity.
Taking into account specific pre-existing factors, it is possible to estimate the risk of diarrhea in hormone receptor-positive and human epidermal growth factor receptor 2-negative - advanced breast cancer patients, candidates for abemaciclib plus endocrine therapy. In these subjects, implementing proactive prevention and adopting a dose-escalation strategy may represent practical approaches to decrease the abemaciclib toxicity burden.
背景/目的：阿贝西利是一种细胞周期蛋白依赖性激酶 4/6 抑制剂，与内分泌治疗联合用于治疗激素受体阳性和人表皮生长因子受体 2 阴性的早期和晚期乳腺癌患者。阿贝西利的安全性特征是频繁发生胃肠道毒性，特别是腹泻。因此，我们对可能与阿贝西利联合内分泌治疗患者腹泻相关的临床因素进行了探索性分析。
选择了可能导致腹泻的潜在因素，如年龄≥70 岁、合并用药和疾病、饮食和泻药使用。这些变量与晚期乳腺癌患者接受阿贝西利治疗时发生 2/3 级腹泻的情况相关。进行了单因素和多因素分析。使用 ROC 曲线测试了敏感性和特异性。
本研究纳入了 80 名晚期乳腺癌女性患者。单因素分析发现，2/3 级腹泻与年龄≥70 岁、多种药物治疗和合并胃肠道疾病之间存在统计学显著相关性（p<0.05）。多因素分析显示，风险因素数量与研究终点显著相关（p<0.0001）。ROC 分析显示，我们的模型具有 82%的敏感性和 75%的特异性。
考虑到特定的预先存在的因素，可以评估激素受体阳性和人表皮生长因子受体 2 阴性的晚期乳腺癌患者接受阿贝西利联合内分泌治疗的腹泻风险。对于这些患者，采取积极的预防措施并采用剂量递增策略可能是降低阿贝西利毒性负担的实用方法。
