Information de reference pour ce titreAccession Number: | 00005407-201701030-00021.
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Author: | Himelstein, Andrew L. MD; Foster, Jared C. PhD; Khatcheressian, James L. MD; Roberts, John D. MD; Seisler, Drew K. BS; Novotny, Paul J. MS; Qin, Rui PhD; Go, Ronald S. MD; Grubbs, Stephen S. MD; O'Connor, Tracey MD; Velasco, Mario R. Jr MD; Weckstein, Douglas MD; O'Mara, Ann PhD; RN; MPH; Loprinzi, Charles L. MD; Shapiro, Charles L. MD
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Institution: | (1)Helen F. Graham Cancer Center & Research Institute, Newark, Delaware (2)Alliance Statistics and Data Center, Mayo Clinic, Rochester, Minnesota (3)Virginia Cancer Institute, Richmond (4)VCU Massey Cancer Center, Richmond, Virginia (5)Now with Yale University, New Haven, Connecticut (6)Now with Regeneron Pharmaceuticals, Basking Ridge, New Jersey (7)Gundersen Health System, La Crosse, Wisconsin (8)Now with Mayo Clinic, Rochester, Minnesota (9)Now with American Society of Clinical Oncology, Alexandria, Virginia (10)Roswell Park Cancer Institute, Buffalo, New York (11)Decatur Memorial Hospital, Decatur, Illinois (12)New Hampshire Oncology Hematology PA, Hooksett (13)Division of Cancer Prevention, National Cancer Institute, Bethesda, Maryland (14)Mayo Clinic, Rochester, Minnesota (15)Icahn School of Medicine at Mount Sinai, New York, New York
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Title: | |
Source: | JAMA. 317(1):48-58, January 3, 2017.
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Abstract: | Importance: Zoledronic acid, a third-generation aminobisphosphonate, reduces the incidence of skeletal-related events and pain in patients with bone metastases. The optimal dosing interval for zoledronic acid is uncertain.
Objective: To determine whether zoledronic acid administered every 12 weeks is noninferior to zoledronic acid administered every 4 weeks.
Design, Setting, Participants: Randomized, open-label clinical trial conducted at 269 academic and community sites in the United States. Patients (n = 1822) with metastatic breast cancer, metastatic prostate cancer, or multiple myeloma who had at least 1 site of bone involvement were enrolled between May 2009 and April 2012; follow-up concluded in April 2014.
Interventions: Patients were randomized to receive zoledronic acid administered intravenously every 4 weeks (n = 911) vs every 12 weeks (n = 911) for 2 years.
Main Outcomes and Measures: The primary end point was the proportion of patients having at least 1 skeletal-related event (defined as clinical fracture, spinal cord compression, radiation to bone, or surgery involving bone) within 2 years after randomization and a between-group absolute difference of 7% as the noninferiority margin. Secondary end points included the proportion of patients with at least 1 skeletal-related event by disease type, pain as assessed by the Brief Pain Inventory (range, 0-10; higher scores indicate worse pain), Eastern Cooperative Oncology Group performance status (range, 0-4; higher scores indicate worse disability), incidence of osteonecrosis of the jaw, kidney dysfunction, skeletal morbidity rate (mean number of skeletal-related events per year), and, in a subset of 553 patients, suppression of bone turnover (assessed by C-terminal telopeptide levels).
Results: Among 1822 patients who were randomized (median age, 65 years; 980 [53.8%] women; 855 with breast cancer, 689 with prostate cancer, and 278 with multiple myeloma), 795 completed the study at 2 years. A total of 260 patients (29.5%) in the zoledronic acid every 4-week dosing group and 253 patients (28.6%) in the every 12-week dosing group experienced at least 1 skeletal-related event within 2 years of randomization (risk difference of -0.3% [1-sided 95% CI, -4% to [infinity]]; P < .001 for noninferiority). The proportions of skeletal-related events did not differ significantly between the every 4-week dosing group vs the every 12-week dosing group for patients with breast cancer, prostate cancer, or multiple myeloma. Pain scores, performance status scores, incidence of jaw osteonecrosis, and kidney dysfunction did not differ significantly between the treatment groups. Skeletal morbidity rates were numerically identical in both groups, but bone turnover was greater (C-terminal telopeptide levels were higher) among patients who received zoledronic acid every 12 weeks.
Conclusions and Relevance: Among patients with bone metastases due to breast cancer, prostate cancer, or multiple myeloma, the use of zoledronic acid every 12 weeks compared with the standard dosing interval of every 4 weeks did not result in an increased risk of skeletal events over 2 years. This longer interval may be an acceptable treatment option.
Trial Registration: clinicaltrials.gov Identifier: NCT00869206
Copyright 2017 by the American Medical Association. All Rights Reserved. Applicable FARS/DFARS Restrictions Apply to Government Use. American Medical Association, 515 N. State St, Chicago, IL 60610.
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References: | 1. Kohno N, Aogi K, Minami H, et al.. Zoledronic acid significantly reduces skeletal complications compared with placebo in Japanese women with bone metastases from breast cancer: a randomized, placebo-controlled trial. J Clin Oncol. 2005;23(15):3314-3321.
2. Saad F, Gleason DM, Murray R, et al.Zoledronic Acid Prostate Cancer Study Group. A randomized, placebo-controlled trial of zoledronic acid in patients with hormone-refractory metastatic prostate carcinoma. J Natl Cancer Inst. 2002;94(19):1458-1468.
3. Pavlakis N, Schmidt R, Stockler M. Bisphosphonates for breast cancer. Cochrane Database Syst Rev. 2005;(3):CD003474.
4. Bamias A, Kastritis E, Bamia C, et al.. Osteonecrosis of the jaw in cancer after treatment with bisphosphonates: incidence and risk factors. J Clin Oncol. 2005;23(34):8580-8587.
5. Novartis Inc. Zometa: prescribing information [December 2005]. http://- ouverture dans une nouvelle fenêtre http://www.accessdata.fda.gov/dr...- ouverture dans une nouvelle fenêtre. Accessed December 6, 2016.
6. Amadori D, Aglietta M, Alessi B, et al.. 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. 2013;14(7):663-670.
7. Hortobagyi GN, Lipton A, Chew HK, et al.. Efficacy and safety of continued zoledronic acid every 4 weeks vs every 12 weeks in women with bone metastases from breast cancer: results of the OPTIMIZE-2 trial. J Clin Oncol. 2014;32(5 suppl):LBA9500^.
8. Oken MM, Creech RH, Tormey DC, et al.. Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol. 1982;5(6):649-655.
9. Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron. 1976;16(1):31-41.
10. Zelen M. The randomization and stratification of patients to clinical trials. J Chronic Dis. 1974;27(7-8):365-375.
11. Cancer Therapy Evaluation Program. Common Terminology Criteria for Adverse Events, Version 3.0. https://ctep.cancer.gov/protocol...- ouverture dans une nouvelle fenêtre. Accessed December 6, 2016.
12. Cleeland CS, Ryan KM. Pain assessment: global use of the Brief Pain Inventory. Ann Acad Med Singapore. 1994;23(2):129-138.
13. Rosen LS, Gordon D, Tchekmedyian NS, et al.. Zoledronic acid versus placebo in the treatment of skeletal metastases in patients with lung cancer and other solid tumors: a phase III, double-blind, randomized trial-the Zoledronic Acid Lung Cancer and Other Solid Tumors Study Group. J Clin Oncol. 2003;21:3150-3157.
14. Lipton A, Zheng M, Seaman J. Zoledronic acid delays the onset of skeletal-related events and progression of skeletal disease in patients with advanced renal cell carcinoma. Cancer. 2003;98(5):962-969.
15. Mantel N. Evaluation of survival data and two new rank order statistics arising in its consideration. Cancer Chemother Rep. 1966;50(3):163-170.
16. Diggle PJ, Liang KY, Zeger SL. Analysis of Longitudinal Data. Oxford, England: Clarendon Press; 1994.
17. National Research Council Panel on Handling Missing Data in Clinical Trials. The Prevention and Treatment of Missing Data in Clinical Trials. Washington, DC: National Academies Press; 2010.
18. Little RJ, D'Agostino R, Cohen ML, et al.. The prevention and treatment of missing data in clinical trials. N Engl J Med. 2012;367(14):1355-1360.
19. US Food and Drug Administration. Denosumab. http://- ouverture dans une nouvelle fenêtre http://www.fda.gov/aboutfda/cent...- ouverture dans une nouvelle fenêtre. Accessed October 26, 2015.
20. Lipton A, Fizazi K, Stopeck AT, et al.. 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. 2012;48(16):3082-3092.
21. Van Poznak CH, Temin S, Yee GC, et al.American Society of Clinical Oncology. American Society of Clinical Oncology executive summary of the clinical practice guideline update on the role of bone-modifying agents in metastatic breast cancer. J Clin Oncol. 2011;29(9):1221-1227.
22. Prevention of symptomatic skeletal events with denosumab administered every 4 weeks vs every 12 weeks. https://clinicaltrials.gov/ct2/s...- ouverture dans une nouvelle fenêtre. Accessed July 19, 2016.
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Language: | English.
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Document Type: | Research: Original Investigation.
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Journal Subset: | Clinical Medicine.
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ISSN: | 0098-7484
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NLM Journal Code: | 7501160
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DOI Number: | https://dx.doi.org/10.1001/jama....- ouverture dans une nouvelle fenêtre
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