Bone Metastases in Breast Cancer

Bone Metastases in Breast Cancer

Allan Lipton
US Oncology Review 2006
Published: October 2008
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Figure 2: Percentage of Patients with at Least One SRE (Excluding Hypercalcemia of Malignancy) in Breast Cancer Patients Treated with either Placebo Versus 90mg Pamidronate or 90mg Pamidronate Versus 4mg Zoledronic Acid

Data from Lipton et al.3 and Rosen et al.9 Adapted with permission from Coleman.6

Results from this study demonstrated that zoledronic acid (4mg) was at least as effective as pamidronate (90mg) in the overall patient population and was significantly more effective at reducing the risk of developing an SRE (by Andersen-Gill analysis) compared with pamidronate in the overall patient population.9,30 Moreover, zoledronic acid demonstrated superiority to pamidronate in the subset of patients with breast cancer.A total of 766 breast cancer patients with bone metastases were randomized to zoledronic acid (4mg via 15-minute infusion) or pamidronate (90mg via two-hour infusion) every three to four weeks for up to 24 months. At the final analysis at 25 months, the percentage of patients who developed at least one SRE was similar between treatment groups (46% for zoledronic acid versus 49% for pamidronate), which is consistent with the results of the placebocontrolled pamidronate trials previously discussed (see Figure 2).3,6,9 However, zoledronic acid consistently reduced the percentage of patients with each type of SRE,16 and the Andersen-Gill multiple event analysis showed that treatment with zoledronic acid significantly reduced the overall risk of experiencing an SRE by an additional 20% compared with pamidronate (hazard ratio=0.799; p=0.025).9 Both zoledronic acid and pamidronate also decreased pain scores in this trial. Among patients with pain scores >0 at baseline, mean composite BPI pain scores decreased from baseline at every time-point up to month 13 (the last time-point assessed) regardless of treatment.30 Moreover, at 25 months, significantly fewer patients treated with zoledronic acid required radiotherapy to bone, which can be considered a surrogate for bone pain, compared with pamidronate (19% versus 27% for pamidronate; p=0.011).16 Importantly, zoledronic acid (4mg) was well tolerated; flu-like symptoms were more common in patients treated with zoledronic acid compared with placebo,but these were mild and occurred primarily after the first infusion.

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References:
  1. Jemal A,Tiwari R C, Murray T et al., "Cancer statistics", CA Cancer J. Clin. (2004), 54: pp. 8-29.
  2. Coleman R E, "Metastatic bone disease: clinical features, pathophysiology and treatment strategies", Cancer Treat Rev. (2001);27: pp. 165-176.
  3. Lipton A,Theriault R L, Hortobagyi G N 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, placebo-controlled trials", Cancer (2000);88: pp. 1,082-1,090.
  4. Coleman R E,"The role of bisphosphonates in breast cancer", The Breast (in press).
  5. Weinfurt K P, Castel L D, Li Y,Timbie J W, Glendenning G A, Schulman K A,"Health-related quality of life among patients with breast cancer receiving zoledronic acid or pamidronate disodium for metastatic bone lesions", Med. Care (2004);42: pp. 164-175.
  6. Coleman R E,"Bisphosphonates: clinical experience", Oncologist (2004);9 (suppl. 4): pp. 14-27.
  7. Hillner B E, Ingle J N, Chlebowski R T, et al., "American Society of Clinical Oncology 2003 update on the role of bisphosphonates and bone health issues in women with breast cancer", [published erratum appears in J. Clin. Oncol. (2004), 22: p. 1,351], J. Clin. Oncol. (2003);21: pp. 4,042-4,057.
  8. Berenson J R, Hillner B E, Kyle R A et al., "American Society of Clinical Oncology clinical practice guidelines: the role of bisphosphonates in multiple myeloma", J. Clin. Oncol. (2002);20: pp. 3,719-3,736.
  9. Rosen L S, Gordon D, Kaminski M et al.,"Long-term efficacy and safety of zoledronic acid compared with pamidronate disodium in the treatment of skeletal complications in patients with advanced multiple myeloma or breast carcinoma.A randomized, doubleblind, multicenter, comparative trial", Cancer (2003);98: pp. 1,735-1,744.
  10. Kohno N, Aogi K, Minami H et al., "A randomized, double-blind, placebo-controlled phase III trial of zoledronic acid in the prevention of skeletal complications in Japanese women with bone metastases from breast cancer [abstract]", Proc.Am. Soc. Clin. Oncol. (2004);23: 43, (abstract 668).
  11. Body J-J,Diel I J, Lichinitser M R et al.,"Intravenous ibandronate reduces the incidence of skeletal complications in patients with breast cancer and bone metastases", Ann. Oncol. (2003);14: pp. 1,399-1,405.
  12. Paterson A H G, Powles T J, Kanis J A, McCloskey E, Hanson J, Ashley S,"Double-blind controlled trial of oral clodronate in patients with bone metastases from breast cancer", J. Clin. Oncol. (1993);11: pp. 59-65.
  13. Kristensen B, Ejlertsen B, Groenvold M, Hein S, Loft H, Mouridsen H T,"Oral clodronate in breast cancer patients with bone metastases: a randomized study", J. Intern. Med. (1999);246: pp. 67-74.
  14. Body J J, Diel I J, Lichinitzer M et al., "Oral ibandronate reduces the risk of skeletal complications in breast cancer patients with metastatic bone disease: results from two randomised, placebo-controlled phase III studies",Br. J.Cancer (2004);90: pp. 1,133-1,137.
  15. Rosen L S, Gordon D H, Dugan W Jr et al.,"Zoledronic acid is superior to pamidronate for the treatment of bone metastases in breast carcinoma patients with at least one osteolytic lesion", Cancer (2004);100: pp. 36-43.
  16. Rosen L S, Coleman R E, Gordon D et al.,"Zoledronic acid is superior to pamidronate in patients with breast cancer and bone metastases [poster]", Presented at: St. Gallen Oncology Conferences: Primary Therapy of Early Breast Cancer 8th International Conference; March 12-15 2003; St Gallen, Switzerland, poster 100.
  17. Williams G, Pazdur R,Temple R,"Assessing tumor-related signs and symptoms to support cancer drug approval", J. Biopharm. Stat. (2004);14: pp. 5-21.
  18. Conte P and Guarneri V, "Safety of intravenous and oral bisphosphonates and compliance with dosing regimens", Oncologist (2004);9 (suppl. 4): pp. 28-37.
  19. Lipton A,"Management of metastatic bone disease and hypercalcemia of malignancy", Am. J. Cancer (2003);2: pp. 427-438.
  20. Powles T, McCloskey E, Kurkilahti M,"Oral clodronate for adjuvant treatment of operable breast cancer: results of a randomized, double-blind, placebo-controlled multicenter trial [abstract]", Proc.Am. Soc. Clin. Oncol. (2004);23: p. 9 (abstract 528).
  21. Saarto T,Vehmanen L, Blomqvist C, Elomaa I, "Ten-year follow-up of a randomized controlled trial of adjuvant clodronate treatment in node-positive breast cancer patients [abstract]", Proc.Am. Soc. Clin. Oncol. (2004);23: p. 8 (abstract 527).
  22. Jaschke A, Bastert G, Solomayer E F, Costa S, Schuetz F, Diel I J,"Adjuvant clodronate treatment improves the overall survival of primary breast cancer patients with micrometastases to bone marrow-a longtime follow-up [abstract]", Proc. Am. Soc. Clin. Oncol. (2004);23: p. 9 (abstract 529).
  23. Hortobagyi G N,Theriault R L, Lipton A, et al.,"Long-term prevention of skeletal complications of metastatic breast cancer with pamidronate", J. Clin. Oncol. (1998);16: pp. 2,038-2,044.
  24. Theriault R L, Lipton A, Hortobagyi G N, et al.,"Pamidronate reduces skeletal morbidity in women with advanced breast cancer and lytic bone lesions: a randomized, placebo-controlled trial", Protocol 18 Aredia Breast Cancer Study Group, J. Clin. Oncol. (1999);17: pp. 846-854.
  25. Diel I J, Body J J, Lichinitser M R et al.,"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 (2004);40: pp. 1,704-1,712.
  26. Body J-J, Diel I, Bell R et al., "Oral ibandronate improves bone pain and preserves quality of life in patients with skeletal metastases due to breast cancer", Pain (2004);111: pp. 306-312.
  27. Rizzoli R, "Bisphosphonates and reduction of skeletal events in patients with bone metastatic breast cancer", Ann. Oncol. (2004);15: pp. 700-701.
  28. Westermann A M,"Intravenous ibandronate reduces the incidence of skeletal complications in patients with breast cancer and bone metastases", Ann. Oncol. (2004);15: pp. 537-538.
  29. Andersen P K, Gill R D, "Cox s regression model for counting processes: a large sample study", Ann. Stat. (1982);10: pp. 1,100-1,120.
  30. Rosen L S, 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. (2001);7: pp. 377-387.
  31. Gnant M, Hausmaninger H, Samonigg H, et al., "Changes in bone mineral density caused by anastrozole or tamoxifen in combination with goserelin (± zoledronate) as adjuvant treatment for hormone receptor-positive premenopausal breast cancer: results of a randomized multicenter trial [abstract]", Presented at: 25th Annual San Antonio Breast Cancer Symposium; December 11-14 2002; San Antonio,Texas (abstract 12).
  32. Theriault R, Jakesz R, Gnant M, Gralow J,"The evolving role of bisphosphonates for the prevention of cancer treatment-induced bone loss in patients with breast cancer [abstract]", Bone (2004);34: pp. S90-S91 (abstract 75).
  33. Coleman R, Rosen L, Zheng M, on behalf of the Study 010 investigators, "Zoledronic acid has long-term efficacy in reducing skeletal complications in patients with bone metastases from breast cancer [abstract]", Presented at: 4th European Breast Cancer Conference, March 16-19 2004; Hamburg, Germany (abstract 246).

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