Abstract
Background
Bisphosphonates are wildly used in breast cancer patients with bone metastasis and generally administrated every 4 weeks to lessen the risk of subsequent skeletal-related events. Bisphosphonates administration every 12 weeks is also recommended in some guidelines. Recent clinical trials suggested that bisphosphonate treatment with reduced frequency (every 12 weeks) to be non-inferior to standard therapy. The object of this analysis was to contrast the efficacy and safety of these two treatment strategies.
Method
We systematically retrieved databases such as MEDLINE, PubMed, Embase, and Cochrane library from 1947 to present for clinical trials comparing the efficacy between standard (every 4 weeks) and de-escalation (every 12 weeks) treatment of bisphosphates.
Results
We identified 4 articles with available data from 4 randomized clinical trials (n = 1721). Administration of bisphosphate every 12 weeks was non-inferior to administration every 4 weeks. There existed no significant difference in on-study skeletal-related events, renal dysfunction, and osteonecrosis of jaw. In the exploratory study, patients who received intravenous bisphosphates before enrollment experienced less on-study skeletal-related events and significant difference was observed between groups.
Conclusion
This analysis suggested that de-escalation treatment with bisphosphates may be superior to standard treatment in terms of efficacy, safety, and economic costs. But it would be better that all the patients receive bisphosphates every 4 weeks for several months before de-escalation.
Similar content being viewed by others
References
Soni A, Ren Z, Hameed O, Chanda D, Morgan CJ, Siegal GP, Wei S (2015) Breast cancer subtypes predispose the site of distant metastases. Am J Clin Pathol 143(4):471–478. https://doi.org/10.1309/AJCPYO5FSV3UPEXS
Awolaran O, Brooks SA, Lavender V (2016) Breast cancer osteomimicry and its role in bone specific metastasis; an integrative, systematic review of preclinical evidence. Breast 30:156–171. https://doi.org/10.1016/j.breast.2016.09.017
Wong MH, Stockler MR, Pavlakis N Bisphosphonates and other bone agents for breast cancer. Cochrane Database Syst Rev (2):CD003474
Van Poznak C, Somerfield MR, Barlow WE, Biermann JS, Bosserman LD, Clemons MJ, Dhesy-Thind SK, Dillmon MS, Eisen A, Frank ES, Jagsi R, Jimenez R, Theriault RL, Vandenberg TA, Yee GC, Moy B (2017) Role of bone-modifying agents in metastatic breast cancer: an American Society of Clinical Oncology-Cancer Care Ontario focused guideline update. J Clin Oncol 35(35):3978–3986. https://doi.org/10.1200/jco.2017.75.4614
Hutton B, Addison CL, Campbell K, Fergusson D, Mazarello S, Clemons M (2013) A systematic review of dosing frequency with bone-targeted agents for patients with bone metastases from breast cancer. J Bone Oncol 2(3):123–131
Ibrahim MFK, Mazzarello S, Shorr R, Vandermeer L, Jacobs C, Hilton J, Hutton B, Clemons M (2015) Should de-escalation of bone-targeting agents be standard of care for patients with bone metastases from breast cancer? A systematic review and meta-analysis. Ann Oncol 26(11):2205–2213
Liu C, Wang L, Liu L, Zhuang J, Tang S, Zhou C, Feng F, Liu R, Zhang J, Zhang T, Gao C, Li H, Li J, Sun C (2018) Efficacy and safety of de-escalation bone-modifying agents for cancer patients with bone metastases: a systematic review and meta-analysis. Cancer Manag Res 10:3809–3823
Awan AA, Hutton B, Hilton J, Mazzarello S, Van Poznak C, Vandermeer L, Bota B, Stober C, Sienkiewicz M, Fergusson D, Shorr R, Clemons M (2019) De-escalation of bone-modifying agents in patients with bone metastases from breast cancer: a systematic review and meta-analysis. Breast Cancer Res Treat
Cao L, Yang YJ, Diao JD, Zhang XH, Liu YL, Wang BY, Li ZW, Liu SX (2017) Systematic review and meta-analysis comparing zoledronic acid administered at 12-week and 4-week intervals in patients with bone metastasis. Oncotarget 8(52):90308–90314. https://doi.org/10.18632/oncotarget.19856
Moher D, Liberati A, Tetzlaff J, Altman DG, Group P (2009) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Open Med 3(3):e123–e130
Higgins JP, Thompson SG (2002) Quantifying heterogeneity in a meta-analysis. Stat Med 21(11):1539–1558. https://doi.org/10.1002/sim.1186
Song F, Sheldon TA, Sutton AJ, Abrams KR, Jones DR (2001) Methods for exploring heterogeneity in meta-analysis. Eval Health Prof 24(2):126–151. https://doi.org/10.1177/016327870102400203
Amadori D, Aglietta M, Alessi B, Gianni L, Ibrahim T, Farina G, Gaion F, Bertoldo F, Santini D, Rondena R, Bogani P, Ripamonti CI (2013) Efficacy and safety of 12-weekly versus 4-weekly zoledronic acid for prolonged treatment of patients with bone metastases from breast cancer (ZOOM): a phase 3, open-label, randomised, non-inferiority trial. Lancet Oncol 14(7):663–670
Amir E, Freedman O, Carlsson L, Dranitsaris G, Tomlinson G, Laupacis A, Tannock IF, Clemons M (2013) Randomized feasibility study of de-escalated (every 12 wk) versus standard (every 3 to 4 wk) intravenous pamidronate in women with low-risk bone metastases from breast cancer. Am J Clin Oncol 36(5):436–442
Himelstein AL, Foster JC, Khatcheressian JL, Roberts JD, Seisler DK, Novotny PJ, Qin R, Go RS, Grubbs SS, O’Connor T, Velasco MR, Weckstein D, O’Mara A, Loprinzi CL, Shapiro CL (2017) Effect of longer-interval vs standard dosing of zoledronic acid on skeletal events in patients with bone metastases: a randomized clinical trial. JAMA 317(1):48–58
Hortobagyi GN, Van Poznak C, Harker WG, Gradishar WJ, Chew H, Dakhil SR, Haley BB, Sauter N, Mohanlal R, Zheng M, Lipton A (2017) Continued treatment effect of zoledronic acid dosing every 12 vs 4 weeks in women with breast cancer metastatic to bone: the OPTIMIZE-2 randomized clinical trial. JAMA Oncology 3(7):906–912
Cockcroft DW, Gault MH (1976) Prediction of creatinine clearance from serum creatinine. Nephron 16(1):31–41. https://doi.org/10.1159/000180580
Rosen LS, Gordon DH, Dugan W Jr, Major P, Eisenberg PD, Provencher L, Kaminski M, Simeone J, Seaman J, Chen BL, Coleman RE (2004) Zoledronic acid is superior to pamidronate for the treatment of bone metastases in breast carcinoma patients with at least one osteolytic lesion. Cancer 100(1):36–43. https://doi.org/10.1002/cncr.11892
Lipton A, Fizazi K, Stopeck AT, Henry DH, Brown JE, Yardley DA, Richardson GE, Siena S, Maroto P, Clemens M, Bilynskyy B, Charu V, Beuzeboc P, Rader M, Viniegra M, Saad F, Ke C, Braun A, Jun S (2012) Superiority of denosumab to zoledronic acid for prevention of skeletal-related events: a combined analysis of 3 pivotal, randomised, phase 3 trials. Eur J Cancer 48(16):3082–3092. https://doi.org/10.1016/j.ejca.2012.08.002
Shapiro CL, Moriarty JP, Dusetzina S, Himelstein AL, Foster JC, Grubbs SS, Novotny PJ, Borah BJ (2017) Cost-effectiveness analysis of monthly zoledronic acid, zoledronic acid every 3 months, and monthly denosumab in women with breast cancer and skeletal metastases: CALGB 70604 (Alliance). J Clin Oncol 35(35):3949–3955
Coleman RE, Rubens RD (1987) The clinical course of bone metastases from breast cancer. Br J Cancer 55(1):61–66. https://doi.org/10.1038/bjc.1987.13
Funding
This work was supported by grants from the National Natural Science Foundation of China (No. 81770875, 81572639), the Science and Technology Department of Sichuan Province (2018SZ0142), the Sichuan University (No. 2018SCUH0093), and the National Clinical Research Center for Geriatrics of West China Hospital (No. Z2018B05), 1.3.5 project for disciplines of excellence, West China Hospital, Sichuan University (ZYGD18022).
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that they have no conflict of interest.
Additional information
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Electronic supplementary material
ESM 1
(DOCX 21 kb)
Rights and permissions
About this article
Cite this article
Yang, M., Yu, X. Management of bone metastasis with intravenous bisphosphonates in breast cancer: a systematic review and meta-analysis of dosing frequency. Support Care Cancer 28, 2533–2540 (2020). https://doi.org/10.1007/s00520-020-05355-7
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00520-020-05355-7