Denosumab in patients with cancer and skeletal metastases: A systematic review and meta-analysis

Cancer Treatment Reviews

Volumn 39, Issue 1, 2013, Pages 97-104

  Peddi, Prashanth ^a   Lopez Olivo, Maria A ^a   Pratt, Gregory F ^a   Suarez Almazor, Maria E ^a  

^a UNIVERSITY OF TEXAS   (United States)

Author keywords

Bisphosphonates (BP); Bone metastases; Denosumab (DB); Skeletal related events (SRE); Zoledronic acid (ZA)

Indexed keywords

ALKALINE PHOSPHATASE BONE ISOENZYME; AMINO TERMINAL TELOPEPTIDE; BISPHOSPHONIC ACID DERIVATIVE; DENOSUMAB; IBANDRONIC ACID; PAMIDRONIC ACID; ZOLEDRONIC ACID;

ACUTE PHASE RESPONSE; BLADDER CANCER; BONE METASTASIS; BONE PAIN; BONE TURNOVER; CANCER MORTALITY; CANCER SURVIVAL; COCHRANE LIBRARY; COLORECTAL CANCER; DRUG EFFICACY; DRUG SAFETY; DRUG WITHDRAWAL; EMBASE; HUMAN; HYPOCALCEMIA; INFECTION; JAW OSTEONECROSIS; LUNG CANCER; MEDLINE; META ANALYSIS; NEOPLASM; NEPHROTOXICITY; OVERALL SURVIVAL; PAIN ASSESSMENT; PATHOLOGIC FRACTURE; PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); QUALITY OF LIFE; RANDOMIZED CONTROLLED TRIAL (TOPIC); REVIEW; SIDE EFFECT; SINGLE DRUG DOSE; SKIN CANCER; SPINAL CORD COMPRESSION; SYSTEMATIC REVIEW; TREATMENT OUTCOME;

ANTIBODIES, MONOCLONAL, HUMANIZED; BONE DENSITY CONSERVATION AGENTS; BONE NEOPLASMS; DIPHOSPHONATES; HUMANS; IMIDAZOLES; NEOPLASMS; RANDOMIZED CONTROLLED TRIALS AS TOPIC;

EID: 84869094189     PISSN: 03057372     EISSN: 15321967     Source Type: Journal    
DOI: 10.1016/j.ctrv.2012.07.002     Document Type: Review

References (60)

1. Coleman R.E. Skeletal complications of malignancy. Cancer 1997, 80:1588-1594.
2. Berenson J.R., Lichtenstein A., Porter L., Dimopoulos M.A., Bordoni R., George S., et al. Long-term pamidronate treatment of advanced multiple myeloma patients reduces skeletal events. Myeloma Aredia Study Group. J Clin Oncol 1998, 16:593-602.
3. Saad F., Gleason D.M., Murray R., Tchekmedyian S., Venner P., Lacombe L., et al. A randomized, placebo-controlled trial of zoledronic acid in patients with hormone-refractory metastatic prostate carcinoma. J Natl Cancer Inst 2002, 94:1458-1468.
4. Johnson J.R., Williams G., Pazdur R. End points and United States food and drug administration approval of oncology drugs. J Clin Oncol 2003, 21:1404-1411.
5. Major P.P., Cook R. Efficacy of bisphosphonates in the management of skeletal complications of bone metastases and selection of clinical endpoints. Am J Clin Oncol 2002, 25:S10-S18.
6. Oefelein M.G., Ricchiuti V., Conrad W., Resnick M.I. Skeletal fractures negatively correlate with overall survival in men with prostate cancer. J Urol 2002, 168:1005-1007.
7. Saad F., Lipton A., Cook R., Chen Y.M., Smith M., Coleman R. Pathologic fractures correlate with reduced survival in patients with malignant bone disease. Cancer 2007, 110:1860-1867.
8. Xie J., Namjoshi M., Wu E.Q., Parikh K., Diener M., Yu A.P., et al. Economic evaluation of denosumab compared with zoledronic acid in hormone-refractory prostate cancer patients with bone metastases. J Manag Care Pharm 2011, 17:621-643.
9. Groot M.T., Boeken Kruger C.G., Pelger R.C., Uyl-de Groot C.A. Costs of prostate cancer, metastatic to the bone, in the Netherlands. Eur Urol 2003, 43:226-232.
10. Delea T., Langer C., McKiernan J., Liss M., Edelsberg J., Brandman J., et al. The cost of treatment of skeletal-related events in patients with bone metastases from lung cancer. Oncology 2004, 67:390-396.
11. Hillner B.E., Ingle J.N., Chlebowski R.T., Gralow J., Yee G.C., Janjan N.A., et al. American Society of Clinical Oncology 2003 update on the role of bisphosphonates and bone health issues in women with breast cancer. J Clin Oncol 2003, 21:4042-4057.
12. Berenson J.R., Hillner B.E., Kyle R.A., Anderson K., Lipton A., Yee G.C., et al. American Society of Clinical Oncology clinical practice guidelines: the role of bisphosphonates in multiple myeloma. J Clin Oncol 2002, 20:3719-3736.
13. Basch E.M., Somerfield M.R., Beer T.M., Carducci M.A., Higano C.S., Hussain M.H., et al. American Society of Clinical Oncology endorsement of the Cancer Care Ontario Practice Guideline on nonhormonal therapy for men with metastatic hormone-refractory (castration-resistant) prostate cancer. J Clin Oncol 2007, 25:5313-5318.
14. Rosen L.S., Gordon D., Tchekmedyian S., Yanagihara R., Hirsh V., Krzakowski M., 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.
15. Ibrahim A., Scher N., Williams G., Sridhara R., Li N., Chen G., et al. Approval summary for zoledronic acid for treatment of multiple myeloma and cancer bone metastases. Clin Cancer Res 2003, 9:2394-2399.
16. Mauri D., Valachis A., Polyzos I.P., Polyzos N.P., Kamposioras K., Pesce L.L. Osteonecrosis of the jaw and use of bisphosphonates in adjuvant breast cancer treatment: a meta-analysis. Breast Cancer Res Treat 2009, 116:433-439.
17. Diel I.J., Bergner R., Grotz K.A. Adverse effects of bisphosphonates: current issues. J Support Oncol 2007, 5:475-482.
18. Silva I., Branco J.C. Rank/Rankl/opg: literature review. Acta Reumatol Port 2011, 36:209-218.
19. Fili S., Karalaki M., Schaller B. Mechanism of bone metastasis: the role of osteoprotegerin and of the host-tissue microenvironment-related survival factors. Cancer Lett 2009, 283:10-19.
20. Jones D.H., Nakashima T., Sanchez O.H., Kozieradzki I., Komarova S.V., Sarosi I., et al. Regulation of cancer cell migration and bone metastasis by RANKL. Nature 2006, 440:692-696.
21. Mancino A.T., Klimberg V.S., Yamamoto M., Manolagas S.C., Abe E. Breast cancer increases osteoclastogenesis by secreting M-CSF and upregulating RANKL in stromal cells. J Surg Res 2001, 100:18-24.
22. Dworkin R.H., Turk D.C., Wyrwich K.W., Beaton D., Cleeland C.S., Farrar J.T., et al. Interpreting the clinical importance of treatment outcomes in chronic pain clinical trials: IMMPACT recommendations. J Pain 2008, 9:105-121.
23. Herr K. Pain assessment strategies in older patients. J Pain 2011, 12:S3-S13.
24. Sterne JAC. Meta-analysis in stata: an updated collection from the stata journal 2009, Stata Press, 3-54, 61, 101-2, 20, 44-5.
25. Kirkova J., Davis M.P., Walsh D., Tiernan E., O'Leary N., LeGrand S.B., et al. Cancer symptom assessment instruments: a systematic review. J Clin Oncol 2006, 24:1459-1473.
26. Coleman R.E., Major P., Lipton A., Brown J.E., Lee K.A., Smith M., et al. Predictive value of bone resorption and formation markers in cancer patients with bone metastases receiving the bisphosphonate zoledronic acid. J Clin Oncol 2005, 23:4925-4935.
27. Coleman R., Costa L., Saad F., Cook R., Hadji P., Terpos E., et al. Consensus on the utility of bone markers in the malignant bone disease setting. Crit Rev Oncol Hematol 2011, 80:411-432.
28. Lipton A., Steger G.G., Figueroa J., Alvarado C., Solal-Celigny P., Body J.J., et al. Randomized active-controlled phase II study of denosumab efficacy and safety in patients with breast cancer-related bone metastases. J Clin Oncol 2007, 25:4431-4437.
29. Berenson J.R., Vescio R., Henick K., Nishikubo C., Rettig M., Swift R.A., et al. A Phase I, open label, dose ranging trial of intravenous bolus zoledronic acid, a novel bisphosphonate, in cancer patients with metastatic bone disease. Cancer 2001, 91:144-154.
30. Higgins J., Green S. Cochrane handbook for systematic reviews of interventions 2011, The Cochrane Collaboration.
31. Stata statistical software: release 11 2009, StataCorp, StataCorp LP, College Station, TX.
32. Body J.J., Facon T., Coleman R.E., Lipton A., Geurs F., Fan M., et al. A study of the biological receptor activator of nuclear factor-kappaB ligand inhibitor, denosumab, in patients with multiple myeloma or bone metastases from breast cancer. Clin Cancer Res 2006, 12:1221-1228.
33. Fizazi K., Lipton A., Mariette X., Body J.J., Rahim Y., Gralow J.R., et al. Randomized phase II trial of denosumab in patients with bone metastases from prostate cancer, breast cancer, or other neoplasms after intravenous bisphosphonates. J Clin Oncol 2009, 27:1564-1571.
34. Stopeck A.T., Lipton A., Body J.J., Steger G.G., Tonkin KdB., Lichinitser R.H., et al. Denosumab compared with zoledronic acid for the treatment of bone metastases in patients with advanced breast cancer: a randomized, double-blind study. J Clin Oncol 2010, 28:5132-5139.
35. Fizazi K., Carducci M., Smith M., Damiao R., Brown J., Karsh L., et al. Denosumab versus zoledronic acid for treatment of bone metastases in men with castration-resistant prostate cancer: a randomised, double-blind study. Lancet 2011, 377:813-822.
36. Henry D.H., Costa L., Goldwasser F., Hirsh V., Hungria V., Prausova J., et al. Randomized, double-blind study of denosumab versus zoledronic acid in the treatment of bone metastases in patients with advanced cancer (excluding breast and prostate cancer) or multiple myeloma. J Clin Oncol 2011, 29:1125-1132.
37. Amgen. XGEVA. Highlights of prescribing information. 2010:Available from: (accessed 04.05.12). http://wwwext.amgen.com/patients/products_xgeva.html.
38. Stopeck A., Fallowfield L., Patrick D., Cleeland C.S., De Boer R.H., Steger G.G., et al. Effects of denosumab versus zoledronic acid (ZA) on pain in patients (pts) with metastatic breast cancer: results from a phase III clinical trial. J Clin Oncol 2010, 28(15 Suppl.):1024.
39. von Moos R., Patrick D., Fallowfield L., Cleeland C.S., Henry D.H., Qian Y., et al. Effects of denosumab versus zoledronic acid (ZA) on pain in patients (pts) with advanced cancer (excluding breast and prostate) or multiple myeloma (MM): results from a randomized phase III clinical trial. J Clin Oncol 2010, (7 Suppl.). abstract 9043.
40. Brown J.E., Cleeland C.S., Fallowfield L.J., Patrick D.L., Fizazi K., Smith M.R., et al. Pain outcomes in patients with bone metastases from castrate-resistant prostate cancer: results from a phase 3 trial of denosumab vs. zoledronic acid. Eur Urol 2011, 10(2 Suppl.):336.
41. Fallowfield L., Patrick D., Body J., Lipton A., Tonkin K.S., Qian Y., et al. Effects of denosumab versus zoledronic acid (ZA) on health-related quality of life (HRQL) in metastatic breast cancer: results from a randomized phase III trial. J Clin Oncol 2010, 28(15 Suppl.):1025.
42. Body J.J., Lipton A., Gralow J., Steger G.G., Gao G., Yeh H., et al. Effects of denosumab in patients with bone metastases with and without previous bisphosphonate exposure. J Bone Miner Res 2010, 25:440-446.
43. Campbell-Baird C., Lipton A., Sarkeshik M., Ma H., Jun S. Incidence of acute phase adverse events following denosumab or intravenous bisphosphonates: results from a randomized, controlled phase II study in patients with breast cancer and bone metastases. Community Oncol 2010, 7:85-89.
44. Clemons M., Cole D.E., Gainford M.C. Can bone markers guide more effective treatment of bone metastases from breast cancer?. Breast Cancer Res Treat 2006, 97:81-90.
45. Lein M., Miller K., Wirth M., Weissbach L., May C., Schmidt K., et al. Bone turnover markers as predictive tools for skeletal complications in men with metastatic prostate cancer treated with zoledronic acid. Prostate 2009, 69:624-632.
46. Yong M., Jensen A.O., Jacobsen J.B., Norgaard M., Fryzek J.P., Sorensen H.T. Survival in breast cancer patients with bone metastases and skeletal-related events: a population-based cohort study in Denmark (1999-2007). Breast Cancer Res Treat 2011, 129:495-503.
47. Sorscher S.M., Lockhart A.C. Ras inhibition and the survival benefit favoring zoledronic acid compared with denosumab in patients with multiple myeloma. J Clin Oncol 2011, 29:2735-2736. author reply 6-8.
48. Croucher P.I., De Hendrik R., Perry M.J., Hijzen A., Shipman C.M., Lippitt J., et al. Zoledronic acid treatment of 5T2MM-bearing mice inhibits the development of myeloma bone disease: evidence for decreased osteolysis, tumor burden and angiogenesis, and increased survival. J Bone Miner Res 2003, 18:482-492.
49. Guenther A., Gordon S., Tiemann M., Burger R., Bakker F., Green J.R., et al. The bisphosphonate zoledronic acid has antimyeloma activity in vivo by inhibition of protein prenylation. Int J Cancer 2010, 126:239-246.
50. Gonzalez-Suarez E., Jacob A.P., Jones J., Miller R., Roudier-Meyer M.P., Erwert R., et al. RANK ligand mediates progestin-induced mammary epithelial proliferation and carcinogenesis. Nature 2010, 468:103-107.
51. Lamoureux F., Moriceau G., Picarda G., Rousseau J., Trichet V., Redini F. Regulation of osteoprotegerin pro- or anti-tumoral activity by bone tumor microenvironment. Biochim Biophys Acta 2010, 1805:17-24.
52. Dougall W.C. Molecular pathways: osteoclast-dependent and osteoclast-independent roles of the RANKL/RANK/OPG Pathway in tumorigenesis and metastasis. Clin Cancer Res 2012, 18:326-335.
53. Miller R.E., Roudier M., Jones J., Armstrong A., Canon J., Dougall W.C. RANK ligand inhibition plus docetaxel improves survival and reduces tumor burden in a murine model of prostate cancer bone metastasis. Mol Cancer Ther 2008, 7:2160-2169.
54. Terpos E., Dimopoulos M.A. Interaction between the skeletal and immune systems in cancer: mechanisms and clinical implications. Cancer Immunol Immunother 2011, 60:305-317.
55. Ferrari-Lacraz S., Ferrari S. Do RANKL inhibitors (denosumab) affect inflammation and immunity?. Osteoporos Int 2011, 22:435-446.
56. Almenoff J.S., Pattishall E.N., Gibbs T.G., DuMouchel W., Evans S.J., Yuen N. Novel statistical tools for monitoring the safety of marketed drugs. Clin Pharmacol Ther 2007, 82:157-166.
57. Abramson E.C., Gajardo H., Kukreja S.C. Hypocalcemia in cancer. Bone Miner 1990, 10:161-169.
58. Dominguez L.J., Di Bella G., Belvedere M., Barbagallo M. Physiology of the aging bone and mechanisms of action of bisphosphonates. Biogerontology 2011, 12:397-408.
59. Luckman S.P., Hughes D.E., Coxon F.P., Graham R., Russell G., Rogers M.J. Nitrogen-containing bisphosphonates inhibit the mevalonate pathway and prevent post-translational prenylation of GTP-binding proteins, including Ras. J Bone Miner Res 1998, 13:581-589.
60. Fizazi K., Bosserman L., Gao G., Skacel T., Markus R. Denosumab treatment of prostate cancer with bone metastases and increased urine N-telopeptide levels after therapy with intravenous bisphosphonates: results of a randomized phase II trial. J Urol 2009, 182:509-515. discussion 15-6.