1. Prediction of severe neutropenia and diarrhoea in breast cancer patients treated with abemaciclib
- Author
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Kiran Shankaran, Ross A. McKinnon, Michael J. Sorich, Andrew Rowland, Sarah Badaoui, Natansh D. Modi, Ashley M. Hopkins, Emily Shaw, Ahmad Y. Abuhelwa, Modi, Natansh D, Abuhelwa, Ahmad Y, Badaoui, Sarah, Shaw, Emily, Shankaran, Kiran, McKinnon, Ross A, Rowland, Andrew, Sorich, Michael J, and Hopkins, Ashley M
- Subjects
Diarrhea ,medicine.medical_specialty ,Neutropenia ,Receptor, ErbB-2 ,Advanced breast ,Aminopyridines ,Breast Neoplasms ,abemaciclib ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Breast cancer ,Internal medicine ,White blood cell ,Antineoplastic Combined Chemotherapy Protocols ,Humans ,Medicine ,neutropenia ,030212 general & internal medicine ,Adverse effect ,Abemaciclib ,RC254-282 ,Aged ,Severe neutropenia ,advanced breast cancer ,business.industry ,Cancer ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,General Medicine ,medicine.disease ,Diarrhoea ,Prediction tool ,diarrhoea ,medicine.anatomical_structure ,chemistry ,030220 oncology & carcinogenesis ,Original Article ,Benzimidazoles ,Female ,Surgery ,Advanced breast cancer ,business ,prediction tool - Abstract
Introduction Neutropenia and diarrhoea are common and potentially serious adverse events associated with abemaciclib in advanced breast cancer (ABC), and the risk factors have been minimally explored. The study aimed to develop clinical prediction tools that allow personalized predictions of neutropenia and diarrhoea following abemaciclib initiation. Materials and methods Data was pooled from MONARCH 1, 2 and 3 trials investigating abemaciclib. Cox proportional hazard analysis was used to assess the association between pre-treatment clinicopathological data and grade ≥3 diarrhoea and neutropenia occurring within the first 365 days of abemaciclib use. Results Older age was associated with increased risk of grade ≥3 diarrhoea [HR [95%CI] for age > 70: 1.72 [1.14–2.58]; P = 0.009]. A clinical prediction tool for abemaciclib induced grade ≥3 neutropenia was optimally defined by race, ECOGPS and white blood cell count. Large discrimination between subgroups was observed; the highest risk subgroup had a 64% probability of grade ≥3 neutropenia within the first 365 days of abemaciclib (150 mg twice daily) + fulvestrant/NSAI, compared to 5% for the lowest risk subgroup. Conclusion The study identified advanced age as significantly associated with an increased risk of abemaciclib induced grade ≥ 3 diarrhoea. A clinical prediction tool, defined by race, ECOGPS and pre-treatment white blood cell count, was able to discriminate subgroups with significantly different risks of grade ≥3 neutropenia following abemaciclib initiation. The tool may enable improved interpretation of personalized risks and the risk-benefit ratio of abemaciclib., Highlights • Neutropenia and diarrhoea are common adverse effects of abemaciclib. • Higher age was associated with abemaciclib induced diarrhoea. • White blood cell count, Race, and performance status were linked with neutropenia. • A prediction tool was developed to provide personalized risks of neutropenia.
- Published
- 2021