Denosumab for the treatment of cancer therapy-induced bone loss and prevention of skeletal-related events in patients with solid tumors

Expert Review of Clinical Pharmacology

Volumn 5, Issue 4, 2012, Pages 359-371

  Lipton, Allan ^a   Balakumaran, Arun ^b  

^a PENN STATE MILTON S HERSHEY MEDICAL CENTER   (United States)

^b AMGEN INC   (United States)

Author keywords

bone metastases; denosumab; skeletal related events; solid tumors

Indexed keywords

AROMATASE INHIBITOR; BISPHOSPHONIC ACID DERIVATIVE; CLODRONIC ACID; DENOSUMAB; IBANDRONIC ACID; PAMIDRONIC ACID; PLACEBO; ZOLEDRONIC ACID;

ABLATION THERAPY; ANEMIA; ARTHRALGIA; BONE DISEASE; BONE MASS; BONE METASTASIS; BONE PAIN; BONE TURNOVER; BREAST CANCER; CANCER HORMONE THERAPY; CANCER THERAPY; CHILL; DOSE RESPONSE; DRUG ABSORPTION; DRUG APPROVAL; DRUG BINDING; DRUG BIOAVAILABILITY; DRUG BLOOD LEVEL; DRUG CLEARANCE; DRUG DISTRIBUTION; DRUG EFFICACY; DRUG HALF LIFE; DRUG MECHANISM; DRUG METABOLISM; DRUG SAFETY; DRUG STRUCTURE; DRUG TOLERABILITY; FATIGUE; FEVER; HUMAN; HYPOCALCEMIA; IC 50; JAW OSTEONECROSIS; LUNG NON SMALL CELL CANCER; METASTASIS; MULTIPLE MYELOMA; NAUSEA; NEPHROTOXICITY; NONHUMAN; OSTEOCLAST; OSTEOCLASTOMA; OSTEOLYSIS; PROSTATE CANCER; REVIEW; SINGLE DRUG DOSE; SOLID TUMOR; VERTEBRA FRACTURE;

ANIMALS; ANTIBODIES, MONOCLONAL, HUMANIZED; BONE NEOPLASMS; BONE RESORPTION; HUMANS; NEOPLASMS; OSTEOCLASTS; RANK LIGAND;

EID: 84866120291     PISSN: 17512433     EISSN: 17512441     Source Type: Journal    
DOI: 10.1586/ecp.12.35     Document Type: Review

References (79)

1. Coleman RE, Lipton A, Roodman GD et al. Metastasis and bone loss: Advancing treatment and prevention. Cancer Treat. Rev. 36(8), 615-620 (2010).
2. Li S, Peng Y, Weinhandl ED et al. Prevalence of recognized bone metastases in the U.S. adult population. J. Clin. Oncol. 29(Suppl.), Abstract 1534 (2011).
3. Coleman RE, Brown JE. Monitoring response to treatment - the role of biomarkers. In: Textbook of Bone Metastases. Jasmin C, Coleman RE, Coia L (Eds). John Wiley and Sons, Hoboken, NJ, USA (2005).
4. Carlin BI, Andriole GL. The natural history, skeletal complications, and management of bone metastases in patients with prostate carcinoma. Cancer 88(Suppl. 12), 2989-2994 (2000).
5. Coleman RE. Skeletal complications of malignancy. Cancer 80(Suppl. 8), 1588-1594 (1997).
6. Selvaggi G, Scagliotti GV. Management of bone metastases in cancer: A review. Crit. Rev. Oncol. Hematol. 56(3), 365-378
7. Buijs JT, van der Pluijm G. Osteotropic cancers: From primary tumor to bone. Cancer Lett. 273(2), 177-193 (2009).
8. Roodman GD. Mechanisms of bone metastasis. N. Engl. J. Med. 350(16), 1655-1664 (2004).
9. Yonou H, Ochiai A, Goya M et al. Intraosseous growth of human prostate cancer in implanted adult human bone: Relationship of prostate cancer cells to osteoclasts in osteoblastic metastatic lesions. Prostate 58(4), 406-413 (2004).
10. Mundy GR. Mechanisms of bone metastasis. Cancer 80(Suppl. 8), 1546-1556 (1997).
11. Mundy GR. Metastasis to bone: Causes, consequences and therapeutic opportunities. Nat. Rev. Cancer 2(8), 584-593 (2002).
12. Kitazawa S, Kitazawa R. RANK ligand is a prerequisite for cancer-associated osteolytic lesions. J. Pathol. 198(2), 228-236 (2002).
13. Major PP, Cook R. Efficacy of bisphosphonates in the management of skeletal complications of bone metastases and selection of clinical endpoints. Am. J. Clin. Oncol. 25(6 Suppl. 1), S10-S18
14. DePuy V, Anstrom KJ, Castel LD, Schulman KA, Weinfurt KP, Saad F. Effects of skeletal morbidities on longitudinal patient-reported outcomes and survival in patients with metastatic prostate cancer. Support. Care Cancer 15(7), 869-876 (2007).
15. Lage MJ, Barber BL, Harrison DJ, Jun S. The cost of treating skeletal-related events in patients with prostate cancer. Am. J. Manag. Care 14(5), 317-322 (2008).
16. Barlev A, Song X, Ivanov B, Setty V, Chung K. Payer costs for inpatient treatment of pathologic fracture, surgery to bone, and spinal cord compression among patients with multiple myeloma or bone metastasis secondary to prostate or breast cancer. J. Manag. Care Pharm. 16(9), 693-702 (2010).
17. 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 bonemodifying agents in metastatic breast cancer. J. Clin. Oncol. 29(9), 1221-1227
18. Russell RG, Watts NB, Ebetino FH, Rogers MJ. Mechanisms of action of bisphosphonates: Similarities and differences and their potential influence on clinical efficacy. Osteoporos. Int. 19(6), 733-759 (2008).
19. Kanis JA, Powles T, Paterson AH, McCloskey EV, Ashley S. Clodronate decreases the frequency of skeletal metastases in women with breast cancer. Bone 19(6), 663-667 (1996).
20. Paterson AH, Powles TJ, Kanis JA, McCloskey E, Hanson J, Ashley S. Double-blind controlled trial of oral clodronate in patients with bone metastases from breast cancer. J. Clin. Oncol. 11(1), 59-65 (1993).
21. McCloskey EV, MacLennan IC, Drayson MT, Chapman C, Dunn J, Kanis JA. A randomized trial of the effect of clodronate on skeletal morbidity in multiple myeloma. MRC Working Party on Leukaemia in Adults. Br. J. Haematol. 100(2), 317-325
22. Body JJ, Diel IJ, Lichinitser MR et al.; MF 4265 Study Group. Intravenous ibandronate reduces the incidence of skeletal complications in patients with breast cancer and bone metastases. Ann. Oncol. 14(9), 1399-1405 (2003).
23. Diel IJ, Body JJ, Lichinitser MR et al.; MF 4265 Study Group. Improved quality of life after long-term treatment with the bisphosphonate ibandronate in patients with metastatic bone disease due to breast cancer. Eur. J. Cancer 40(11), 1704-1712
24. Body JJ, Diel IJ, Bell R et al. Oral ibandronate improves bone pain and preserves quality of life in patients with skeletal metastases due to breast cancer. Pain 111(3), 306-312 (2004).
25. Elomaa I, Kylmälä T, Tammela T et al. Effect of oral clodronate on bone pain. A controlled study in patients with metastic prostatic cancer. Int. Urol. Nephrol. 24(2), 159-166 (1992).
26. Ernst DS, Tannock IF, Winquist EW et al. Randomized, double-blind, controlled trial of mitoxantrone/prednisone and clodronate versus mitoxantrone/prednisone and placebo in patients with hormonerefractory prostate cancer and pain. J. Clin. Oncol. 21(17), 3335-3342 (2003).
27. Hortobagyi GN, Theriault RL, Lipton A et al. Long-term prevention of skeletal complications of metastatic breast cancer with pamidronate. Protocol 19 Aredia Breast Cancer Study Group. J. Clin. Oncol. 16(6), 2038-2044 (1998).
28. Hortobagyi GN, Theriault RL, Porter L et al. Efficacy of pamidronate in reducing skeletal complications in patients with breast cancer and lytic bone metastases. Protocol 19 Aredia Breast Cancer Study Group. N. Engl. J. Med. 335(24), 1785-1791 (1996).
29. Theriault RL, Lipton A, Hortobagyi GN et al. Pamidronate reduces skeletal morbidity in women with advanced breast cancer and lytic bone lesions: A randomized, placebocontrolled trial. Protocol 18 Aredia Breast Cancer Study Group. J. Clin. Oncol. 17(3), 846-854 (1999).
30. Berenson JR, Lichtenstein A, Porter L et al. Long-term pamidronate treatment of advanced multiple myeloma patients reduces skeletal events. Myeloma Aredia Study Group. J. Clin. Oncol. 16(2), 593-602 (1998).
31. Berenson JR, Lichtenstein A, Porter L et al. Efficacy of pamidronate in reducing skeletal events in patients with advanced multiple myeloma. Myeloma Aredia Study Group. N. Engl. J. Med. 334(8), 488-493
32. Cartenì G, Bordonaro R, Giotta F et al. Efficacy and safety of zoledronic acid in patients with breast cancer metastatic to bone: A multicenter clinical trial. Oncologist 11(7), 841-848 (2006).
33. 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. 23(15), 3314-3321 (2005).
34. Lipton A, Cook RJ, Major P, Smith MR, Coleman RE. Zoledronic acid and survival in breast cancer patients with bone metastases and elevated markers of osteoclast activity. Oncologist 12(9), 1035-1043 (2007).
35. Rosen LS, Gordon D, Kaminski M et al. Zoledronic acid versus pamidronate in the treatment of skeletal metastases in patients with breast cancer or osteolytic lesions of multiple myeloma: A Phase III, double-blind, comparative trial. Cancer J. 7(5), 377-387 (2001).
36. Rosen LS, Gordon D, Tchekmedyian NS et al. Long-term efficacy and safety of zoledronic acid in the treatment of skeletal metastases in patients with non-small-cell lung carcinoma and other solid tumors: A randomized, Phase III, double-blind, placebo-controlled trial. Cancer 100(12), 2613-2621 (2004).
37. Rosen LS, Gordon D, Tchekmedyian S 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. 21(16), 3150-3157 (2003).
38. 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. 94(19), 1458-1468 (2002).
39. Saad F, Gleason DM, Murray R et al.; Zoledronic Acid Prostate Cancer Study Group. Long-term efficacy of zoledronic acid for the prevention of skeletal complications in patients with metastatic hormone-refractory prostate cancer. J. Natl Cancer Inst. 96(11), 879-882 (2004).
40. Wardley A, Davidson N, Barrett-Lee P et al. Zoledronic acid significantly improves pain scores and quality of life in breast cancer patients with bone metastases: A randomised, crossover study of community vs hospital bisphosphonate administration. Br. J. Cancer 92(10), 1869-1876 (2005).
41. Kleber M, Cybulla M, Bauchmüller K, Ihorst G, Koch B, Engelhardt M. Monitoring of renal function in cancer patients: An ongoing challenge for clinical practice. Ann. Oncol. 18(5), 950-958
42. Launay-Vacher V, Oudard S, Janus N et al.; Renal Insufficiency and Cancer Medications (IRMA) Study Group. Prevalence of renal insufficiency in cancer patients and implications for anticancer drug management: The Renal Insufficiency and Anticancer Medications (IRMA) study. Cancer 110(6), 1376-1384 (2007).
43. Barrett-Lee P, Bloomfield D, Dougherty L et al. An audit to determine the time taken to administer intravenous bisphosphonate infusions in patients diagnosed with metastatic breast cancer to bone in a hospital setting. Curr. Med. Res. Opin. 23(7), 1575-1582 (2007).
44. Richhariya A, Qian Y, Zhao Y, Chung K. Time associated with intravenous zoledronic acid administration in patients with breast or prostate cancer and bone metastasis. Cancer Manag. Res. 4, 55-60 (2012).
45. Ellis GK, Bone HG, Chlebowski R et al. Randomized trial of denosumab in patients receiving adjuvant aromatase inhibitors for nonmetastatic breast cancer. J. Clin. Oncol. 26(30), 4875-4882
46. Smith MR, Egerdie B, Hernández Toriz N et al.; Denosumab HALT Prostate Cancer Study Group. Denosumab in men receiving androgen-deprivation therapy for prostate cancer. N. Engl. J. Med. 361(8), 745-755
47. Kostenuik PJ, Nguyen HQ, McCabe J et al. Denosumab, a fully human monoclonal antibody to RANKL, inhibits bone resorption and increases BMD in knock-in mice that express chimeric (murine/human) RANKL. J. Bone Miner. Res. 24(2), 182-195
48. Doshi S, Sutjandra L, Zheng J et al. Denosumab dose selection for preventing skeletal related events in patients with solid tumors. Clin. Can. Res. 18(9), 2648-2657
49. Gibiansky L, Sutjandra L, Doshi S et al. Population pharmacokinetic analysis of denosumab in advanced cancer patients with solid tumors. Clin. Pharmacokinet. 51(4), 247-260
50. Yonemori K, Fujiwara Y, Minami H et al. Phase 1 trial of denosumab safety, pharmacokinetics, and pharmacodynamics in Japanese women with breast cancerrelated bone metastases. Cancer Sci. 99(6), 1237-1242 (2008).
51. Fizazi K, Lipton A, Mariette X 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. 27(10), 1564-1571 (2009).
52. Bone HG, Bolognese MA, Yuen CK et al. Effects of denosumab treatment and discontinuation on bone mineral density and bone turnover markers in postmenopausal women with low bone mass. J. Clin. Endocrinol. Metab. 96(4), 972-980 (2011).
53. Miller PD, Bolognese MA, Lewiecki EM et al.; Amg Bone Loss Study Group. Effect of denosumab on bone density and turnover in postmenopausal women with low bone mass after long-term continued, discontinued, and restarting of therapy: A randomized blinded Phase 2 clinical trial. Bone 43(2), 222-229
54. Brown JP, Dempster DW, Ding B et al. Bone remodeling in postmenopausal women who discontinued denosumab treatment: off-treatment biopsy study. J. Bone Miner. Res. 26(11), 2737-2744
55. Jamal SA, Ljunggren O, Stehman-Breen C et al. Effects of denosumab on fracture and bone mineral density by level of kidney function. J. Bone Miner. Res. 26(8), 1829-1835 (2011).
56. Body JJ, Facon T, Coleman RE et al. A study of the biological receptor activator of nuclear factor-κB ligand inhibitor, denosumab, in patients with multiple myeloma or bone metastases from breast cancer. Clin. Cancer Res. 12(4), 1221-1228
57. Lipton A, Steger GG, Figueroa 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. 25(28), 4431-4437 (2007).
58. Lipton A, Steger GG, Figueroa J et al. Extended efficacy and safety of denosumab in breast cancer patients with bone metastases not receiving prior bisphosphonate therapy. Clin. Cancer Res. 14(20), 6690-6696 (2008).
59. Stopeck AT, Lipton A, Body JJ 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. 28(35), 5132-5139
60. Fizazi K, Carducci M, Smith M et al. A randomised, double-blind study of denosumab versus zoledronic acid in the treatment of bone metastases in men with castration-resistant prostate cancer. Lancet 377, 813-822 (2011).
61. Henry DH, Costa L, Goldwasser F 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. 29(9), 1125-1132
62. Henry DH, Von Moos R, Hungria V et al. Delaying skeletal-related events in a randomized Phase III study of denosumab versus zoledronic acid in patients with advanced cancer. J. Clin. Oncol. 28(Suppl.), Abstract 9133
63. Lipton A, Siena S, Rader M et al. Comparison of denosumab versus zoledronic acid (ZA) for treatment of bone metastases in advanced cancer patients: An integrated analysis of 3 pivotal trials. Ann. Oncol. 21(Suppl. 8), viii380, Abstract 1249P (2010).
64. Cleeland CS, Patrick DL, Fallowfield L et al. Effects of denosumab vs zoledronic zcid (ZA) on pain in patients (Pts) with advanced cancer and bone metastases: An integrated analysis of 3 pivotal trials. Ann. Oncol. 21(Suppl. 8), viii380 (2010).
65. Ellis GK, Bone HG, Chlebowski R et al. Effect of denosumab on bone mineral density in women receiving adjuvant aromatase inhibitors for non-metastatic breast cancer: Subgroup analyses of a Phase 3 study. Breast Cancer Res. Treat. 118(1), 81-87 (2009).
66. Smith MR, Saad F, Egerdie B et al. Effects of denosumab on bone mineral density in men receiving androgen deprivation therapy for prostate cancer. J. Urol. 182(6), 2670-2675 (2009).
67. Lipton A, Fizazi K, Stopeck A et al. Prevention of skeletal-related events with denosumab or zoledronic acid: Combined analysis from 3 registrational trials. Eur. J. Cancer 47(Suppl. 1), 268
68. Saad F, Brown JE, Van Poznak C et al. Incidence, risk factors, and outcomes of osteonecrosis of the jaw: Integrated analysis from three blinded active-controlled Phase III trials in cancer patients with bone metastases. Ann. Oncol. 23(5), 1341-1347
69. Smith MR, Saad F, Coleman R et al. Denosumab and bone-metastasis-free survival in men with castrationresistant prostate cancer: Results of a Phase 3, randomised, placebocontrolled trial. Lancet 379(9810), 39-46
70. Kantoff PW, Higano CS, Shore ND et al.; IMPACT Study Investigators. Sipuleucel-T immunotherapy for castration-resistant prostate cancer. . ngl. J. Med. 363(5), 411-422 (2010).
71. Lipton A, Theriault RL, Hortobagyi GN et al. Pamidronate prevents skeletal complications and is effective palliative treatment in women with breast carcinoma and osteolytic bone metastases: Long term follow-up of two randomized, placebocontrolled trials. Cancer 88(5), 1082-1090
72. Miller K, Wang M, Gralow J et al. Paclitaxel plus bevacizumab versus paclitaxel alone for metastatic breast cancer. N. Engl. J. Med. 357(26), 2666-2676 (2007).
73. Sandler A, Gray R, Perry MC et al. Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. N. Engl. J. Med. 355(24), 2542-2550 (2006).
74. Thomas D, Henshaw R, Skubitz K et al. Denosumab in patients with giant-cell tumour of bone: An open-label, Phase 2 study. Lancet Oncol. 11(3), 275-280
75. Goss PE, Barrios CH, Bell R et al. A randomized, double-blind, placebocontrolled multicenter Phase III study comparing denosumab with placebo as adjuvant treatment for women with early-stage breast cancer who are at high risk of disease recurrence (D-CARE). J. Clin. Oncol. 29(Suppl.), Abstract TPS152 (2011).
76. Blay J, Chawla SP, Martin Broto J et al. Denosumab safety and efficacy in giant cell tumor of bone (GCTB): Interim results from a Phase II study. J. Clin. Oncol. 29(Suppl.), Abstract 10034
77. Gonzalez-Suarez E, Jacob AP, Jones J et al. RANK ligand mediates progestin-induced mammary epithelial proliferation and carcinogenesis. Nature 468(7320), 103-107 (2010).
78. Hu MI, Gucalp R, Insogna K et al. Denosumab for treatment of hypercalcemia of malignancy in patients with solid tumors or hematological malignancies refractory to IV bisphosphonates: A single-arm multicenter study Blood (2011).
79. Boyce AM, Yao J, Kelly MH et al. Denosumab treatment of fibrous dysplasia of bone. J. Bone Miner. Res. 27(7), 1462-1470 (2012).