Abemaciclib-associated Diarrhea: An Exploratory Analysis of Real-life Data.

Vittorio Gebbia, Federica Martorana, Maria Vita Sanò, Maria Rosaria Valerio, Francesco Giotta, Massimiliano Spada, Dario Piazza, Michele Caruso, Paolo Vigneri

Journal: Anticancer research 2023;43(3):1291-1299

PMID: 36854501

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Abstract

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.

PATIENTS AND METHODS

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.

RESULTS

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.

CONCLUSION

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.

Address: 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; [email protected] [email protected].; Department of Clinical and Experimental Medicine, University of Catania, and Center of Experimental Oncology and Hematology AOU, Policlinico "G. Rodolico - San Marco", Catania, Italy.; Medical Oncology Unit, Istituto Clinico Humanitas, Catania, Italy.; Medical Oncology Unit, Policlinico "P. Giaccone", University of Palermo, Palermo, Italy.; Medical Oncology Unit, Istituto Tumori "Giovanni Paolo II", IRCSS, Bari, Italy.; Medical Oncology Unit, Fondazione Giglio, Ospedale di Cefalù, Palermo, Italy.; 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.

DOI: 10.21873/anticanres.16276

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MeSH Terms: Humans, Female, Aged, Diarrhea, Aminopyridines, Benzimidazoles, Breast Neoplasms