1. An open label, randomized phase 2 trial assessing the impact of food on the tolerability of abemaciclib in patients with Advanced Breast Cancer
- Author
-
Elgene Lim, Frances Boyle, Meena Okera, Sherene Loi, Sema Sezgin Goksu, Gertjan van Hal, Sonya C. Chapman, Jonathon Colby Gable, Yanyun Chen, Gregory L. Price, Anwar M. Hossain, M. Corona Gainford, Meritxell Bellet Ezquerra, Institut Català de la Salut, [Lim E] Garvan Institute of Medical Research, St. Vincent’s Clinical School, University of New South Wales, Darlinghurst, NSW, Australia. [Boyle F] Mater Hospital, North Sydney, NSW, Australia. [Okera M] Adelaide Cancer Centre, Kurralta Park, SA, Australia. [Loi S] Peter MacCallum Cancer Centre, Melbourne, VI, Australia. [Sezgin Goksu S] Akdeniz University Medical Faculty, Antalya, Turkey. [van Hal G] Eli Lilly and Company, Utrecht, Netherlands. [Bellet Ezquerra M] Vall d’Hebron Hospital Universitari, Barcelona, Spain. Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain, and Vall d'Hebron Barcelona Hospital Campus
- Subjects
Diarrhea ,Cancer Research ,neoplasias::neoplasias por localización::neoplasias de la mama [ENFERMEDADES] ,Pathological Conditions, Signs and Symptoms::Signs and Symptoms::Signs and Symptoms, Digestive::Diarrhea [DISEASES] ,afecciones patológicas, signos y síntomas::signos y síntomas::signos y síntomas digestivos::diarrea [ENFERMEDADES] ,Neoplasms::Neoplasms by Site::Breast Neoplasms [DISEASES] ,Otros calificadores::Otros calificadores::/inducido químicamente [Otros calificadores] ,Aminopyridines ,Otros calificadores::Otros calificadores::/farmacoterapia [Otros calificadores] ,Breast Neoplasms ,Other subheadings::Other subheadings::/drug therapy [Other subheadings] ,Loperamide ,Medicaments antineoplàstics - Efectes secundaris ,Oncology ,Antineoplastic Combined Chemotherapy Protocols ,Mama - Càncer - Tractament ,Other subheadings::Other subheadings::/chemically induced [Other subheadings] ,Humans ,Benzimidazoles ,Female ,Diarrea - Abstract
Breast cancer; CDK4/6 inhibitor; Tolerability Cáncer de mama; Inhibidor de CDK4/6; Tolerabilidad Càncer de mama; Inhibidor de CDK4/6; Tolerabilitat Purpose Abemaciclib, a CDK4 & 6 inhibitor, is indicated for advanced breast cancer treatment. Diarrhea is a frequently associated adverse event of abemaciclib. The study objective was to investigate if food intake impacts local gastrointestinal toxicity. Methods This Phase 2 study (I3Y-MC-JPCP, NCT03703466) randomized 72 patients 1:1:1 to receive abemaciclib 200 mg monotherapy twice daily (1) with a meal, (2) in a modified fasting state or (3) without regard to food. Primary endpoints included: incidence of investigator assessed severe (≥ Grade 3), prolonged (> 7 days) Grade 2 diarrhea, treatment discontinuation, dose modifications, and loperamide utilization during the first 3 cycles of treatment. Patient outcomes were captured via a daily electronic diary. Pharmacokinetics (PK) are reported. Results Incidence of investigator assessed severe diarrhea (Grade ≥ 3) was 1.4% (1 patient in Arm 1). Median duration of Grade 3 diarrhea was 1 day by both investigator assessment (1 patient in Arm 1) and patient-reported assessment (1 patient each in Arms 1 and 3). Median duration of investigator-assessed Grade 2 diarrhea was 2 days overall. No patient discontinued treatment due to diarrhea. Nine patients (12.7%) had a dose reduction, and 7 patients (9.9%) had a dose omission due to diarrhea. Ninety-four percent of patients used loperamide at least once. Abemaciclib PK was comparable across the 3 arms. Conclusion The results suggest that diarrhea incidence associated with abemaciclib was unrelated to timing of food intake, was predominantly low grade, of short duration and well managed with loperamide and dose modifications. Open Access funding enabled and organized by CAUL and its Member Institutions. The authors are grateful to the patients, their families, and caregivers for participating in study JPCP, and to the study investigator and site staff for their collaboration. Writing and editing provided by Nicholas Pulliam, Sandra Deady and John Hurley of Eli Lilly and Company. Funding provided by Eli Lilly and Company.
- Published
- 2022
- Full Text
- View/download PDF