M F K Ibrahim1, S Mazzarello2, R Shorr3, L Vandermeer2, C Jacobs1, J Hilton4, B Hutton2, M Clemons5. 1. Department of Medicine and Division of Medical Oncology, The Ottawa Hospital. 2. Ottawa Hospital Research Institute and Department of Medicine, University of Ottawa. 3. The Ottawa General Hospital, Ottawa, Canada. 4. Department of Medicine and Division of Medical Oncology, The Ottawa Hospital Ottawa Hospital Research Institute and Department of Medicine, University of Ottawa. 5. Department of Medicine and Division of Medical Oncology, The Ottawa Hospital Ottawa Hospital Research Institute and Department of Medicine, University of Ottawa mclemons@toh.on.ca.
Abstract
BACKGROUND: De-escalation of bone-targeted agents, such as bisphosphonates and denosumab, from 4- to 12-weekly dosing is an increasingly used strategy in patients with bone metastases from breast cancer. It is unclear whether there is sufficient evidence to support de-escalation as a standard of care. METHODS: A systematic review of randomized trials comparing standard 4-weekly administration of bone-targeted agents with de-escalated (Q12-weekly) dosing in breast cancer patients was carried out. Medline, PubMed and the Cochrane Register of Controlled Trials were searched from inception until November 2014 for relevant studies. Outcomes of interest included skeletal-related event (SRE) rates, bone pain, adverse events (AEs) and bone turnover biomarkers. Random-effects meta-analyses were carried out. RESULTS: A total of nine citations representing seven unique studies were eligible. One study is ongoing with no reported data. Six studies reported data for at least one outcome of interest. Data were available comparing standard versus de-escalated therapy for pamidronate (1 study, 38 patients), zoledronate (3 studies, 1117 patients) and denosumab (2 studies, 284 patients). Meta-analysis of five trials reporting data for on-study SRE rates between standard (61/443 patients) and de-escalated (49/392 patients) arms produced a summary risk ratio of 0.90 (95% confidence interval 0.63-1.29). Meta-analyses of data for AEs and bone turnover biomarkers also showed no statistically significant differences between standard and de-escalated arms, though only limited numbers of patients and events were present for most analyses. CONCLUSION: In this systematic review of studies of bisphosphonates and denosumab, there appears to be no difference in SREs or pain with de-escalated therapy. While a large, hopefully definitive study is ongoing, the data presented so far are consistent with de-escalation of bone-targeting agents becoming a standard of care for patients with bone metastases from breast cancer.
BACKGROUND: De-escalation of bone-targeted agents, such as bisphosphonates and denosumab, from 4- to 12-weekly dosing is an increasingly used strategy in patients with bone metastases from breast cancer. It is unclear whether there is sufficient evidence to support de-escalation as a standard of care. METHODS: A systematic review of randomized trials comparing standard 4-weekly administration of bone-targeted agents with de-escalated (Q12-weekly) dosing in breast cancerpatients was carried out. Medline, PubMed and the Cochrane Register of Controlled Trials were searched from inception until November 2014 for relevant studies. Outcomes of interest included skeletal-related event (SRE) rates, bone pain, adverse events (AEs) and bone turnover biomarkers. Random-effects meta-analyses were carried out. RESULTS: A total of nine citations representing seven unique studies were eligible. One study is ongoing with no reported data. Six studies reported data for at least one outcome of interest. Data were available comparing standard versus de-escalated therapy for pamidronate (1 study, 38 patients), zoledronate (3 studies, 1117 patients) and denosumab (2 studies, 284 patients). Meta-analysis of five trials reporting data for on-study SRE rates between standard (61/443 patients) and de-escalated (49/392 patients) arms produced a summary risk ratio of 0.90 (95% confidence interval 0.63-1.29). Meta-analyses of data for AEs and bone turnover biomarkers also showed no statistically significant differences between standard and de-escalated arms, though only limited numbers of patients and events were present for most analyses. CONCLUSION: In this systematic review of studies of bisphosphonates and denosumab, there appears to be no difference in SREs or pain with de-escalated therapy. While a large, hopefully definitive study is ongoing, the data presented so far are consistent with de-escalation of bone-targeting agents becoming a standard of care for patients with bone metastases from breast cancer.
Authors: Brian Younho Hong; Mohammed F K Ibrahim; Ricardo Fernandes; Sasha Mazzarello; Brian Hutton; Risa Shorr; Mark Clemons Journal: Curr Oncol Date: 2016-02-18 Impact factor: 3.677
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Authors: Sharon McGee; Mashari AlZahrani; Carol Stober; Terry L Ng; Katherine Cole; Gail Larocque; Arif Awan; Sandeep Sehdev; John Hilton; Lisa Vandermeer; Brian Hutton; Gregory Pond; Deanna Saunders; Mark Clemons Journal: J Bone Oncol Date: 2021-02-19 Impact factor: 4.072
Authors: Ricardo Fernandes; Peter Siegel; Svetlana Komarova; John Hilton; Christina Addison; Mohammed F K Ibrahim; Joel Werier; Kristopher Dennis; Gurmit Singh; Eitan Amir; Virginia Jarvis; Urban Emmenegger; Sasha Mazzarello; Mark Clemons Journal: J Bone Oncol Date: 2016-02-23 Impact factor: 4.072