M Clemons1, D Fergusson2, D Simos3, M Mates4, A Robinson4, N Califaretti5, L Zibdawi3, M Bahl5, J Raphael6, M F K Ibrahim7, R Fernandes8, L Pitre9, O Aseyev7, C Stober10, L Vandermeer10, D Saunders10, B Hutton11, R Mallick11, G R Pond12, A Awan13, J Hilton14. 1. Division of Medical Oncology, Department of Medicine, The Ottawa Hospital and University of Ottawa, Ottawa, Canada; Cancer Therapeutics Program, Ottawa Hospital Research Institute, Ottawa, Canada; Clinical Epidemiology Program, The Ottawa Hospital Research Institute, Ottawa, Canada. Electronic address: mclemons@toh.ca. 2. Division of Clinical Epidemiology, Department of Medicine, The Ottawa Hospital and University of Ottawa, Ottawa, Canada; Clinical Epidemiology Program, The Ottawa Hospital Research Institute, Ottawa, Canada. 3. The Stronach Regional Cancer Center, Newmarket, Canada. 4. Cancer Centre of Southeastern Ontario, Kingston, Canada. 5. Grand River Regional Cancer Centre, Kitchener, Canada. 6. Department of Medical Oncology, Schulich School of Medicine & Dentistry, Western University and London Health Sciences Centre, London, Canada; Division of Medical Oncology, London Regional Cancer Program, Western University, London, Canada. 7. Thunder Bay Regional Health Research Institute, Thunder Bay, Canada. 8. Department of Medical Oncology, Schulich School of Medicine & Dentistry, Western University and London Health Sciences Centre, London, Canada. 9. The Northeast Cancer Centre, Sudbury, Canada. 10. Cancer Therapeutics Program, Ottawa Hospital Research Institute, Ottawa, Canada. 11. Clinical Epidemiology Program, The Ottawa Hospital Research Institute, Ottawa, Canada. 12. McMaster University, Hamilton, Canada. 13. Division of Medical Oncology, Department of Medicine, The Ottawa Hospital and University of Ottawa, Ottawa, Canada. 14. Division of Medical Oncology, Department of Medicine, The Ottawa Hospital and University of Ottawa, Ottawa, Canada; Cancer Therapeutics Program, Ottawa Hospital Research Institute, Ottawa, Canada.
Abstract
BACKGROUND: The optimal duration of filgrastim as primary febrile neutropenia (FN) prophylaxis in early breast cancer patients is unknown, with 5, 7 or 10 days being commonly prescribed. This trial evaluates whether 5 days of filgrastim was non-inferior to 7/10 days. PATIENTS AND METHODS: In this randomised, open-label trial, early breast cancer patients who were to receive filgrastim as primary FN prophylaxis were randomly allocated to 5 versus 7 versus 10 days of filgrastim for all chemotherapy cycles. A protocol amendment in November 2017 allowed subsequent patients (N = 324) to be randomised to either 5 or 7/10 days. The primary outcome was a composite of either FN or treatment-related hospitalisations. Secondary outcomes included chemotherapy dose reductions, delays and discontinuations. Analyses were carried out by per protocol (primary) and intention-to-treat, and the non-inferiority margin was set at 3% for the risk of having FN and/or hospitalisation per cycle of chemotherapy. RESULTS:Patients (N = 466) were randomised to receive 5 (184, 39.5%), or 7/10 (282, 60.5%) days of filgrastim. In our primary analysis, the difference in risk of either FN or treatment-related hospitalisation per cycle was -1.52% [95% confidence interval (CI): -3.22% to 0.19%] suggesting non-inferiority of a 5-day filgrastim schedule compared with 7/10-days. The difference in events per cycle for FN was 0.11% (95% CI: -1.05 to 1.27) while for treatment-related hospitalisations it was -1.68% (95% CI: -2.73% to -0.63%). The overall proportions of patients having at least one occurrence of either FN or treatment-related hospitalisation were 11.8% and 14.96% for the 5- and 7/10-day groups, respectively (risk difference: -3.17%, 95% CI: -9.51% to 3.18%). CONCLUSION: Five days of filgrastim was non-inferior to 7/10 days. Given the cost and toxicity of this agent, 5 days should be considered standard of care. CLINICALTRIALS. GOV REGISTRATION: NCT02428114 and NCT02816164.
RCT Entities:
BACKGROUND: The optimal duration of filgrastim as primary febrile neutropenia (FN) prophylaxis in early breast cancerpatients is unknown, with 5, 7 or 10 days being commonly prescribed. This trial evaluates whether 5 days of filgrastim was non-inferior to 7/10 days. PATIENTS AND METHODS: In this randomised, open-label trial, early breast cancerpatients who were to receive filgrastim as primary FN prophylaxis were randomly allocated to 5 versus 7 versus 10 days of filgrastim for all chemotherapy cycles. A protocol amendment in November 2017 allowed subsequent patients (N = 324) to be randomised to either 5 or 7/10 days. The primary outcome was a composite of either FN or treatment-related hospitalisations. Secondary outcomes included chemotherapy dose reductions, delays and discontinuations. Analyses were carried out by per protocol (primary) and intention-to-treat, and the non-inferiority margin was set at 3% for the risk of having FN and/or hospitalisation per cycle of chemotherapy. RESULTS:Patients (N = 466) were randomised to receive 5 (184, 39.5%), or 7/10 (282, 60.5%) days of filgrastim. In our primary analysis, the difference in risk of either FN or treatment-related hospitalisation per cycle was -1.52% [95% confidence interval (CI): -3.22% to 0.19%] suggesting non-inferiority of a 5-day filgrastim schedule compared with 7/10-days. The difference in events per cycle for FN was 0.11% (95% CI: -1.05 to 1.27) while for treatment-related hospitalisations it was -1.68% (95% CI: -2.73% to -0.63%). The overall proportions of patients having at least one occurrence of either FN or treatment-related hospitalisation were 11.8% and 14.96% for the 5- and 7/10-day groups, respectively (risk difference: -3.17%, 95% CI: -9.51% to 3.18%). CONCLUSION: Five days of filgrastim was non-inferior to 7/10 days. Given the cost and toxicity of this agent, 5 days should be considered standard of care. CLINICALTRIALS. GOV REGISTRATION: NCT02428114 and NCT02816164.
Authors: Arif Awan; Bassam Basulaiman; Carol Stober; Mark Clemons; Dean Fergusson; John Hilton; Waleed Al Ghareeb; Rachel Goodwin; Mohammed Ibrahim; Brian Hutton; Lisa Vandermeer; Ranjeeta Mallick; Michael M Vickers Journal: Health Sci Rep Date: 2021-12-14
Authors: Susan Dent; Dean Fergusson; Olexiy Aseyev; Carol Stober; Gregory Pond; Arif A Awan; Sharon F McGee; Terry L Ng; Demetrios Simos; Lisa Vandermeer; Deanna Saunders; John F Hilton; Brian Hutton; Mark Clemons Journal: Curr Oncol Date: 2021-12-03 Impact factor: 3.677