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Bone complications* can have a devastating impact 
on patients and their families.1-5

*Bone complications, also known as skeletal-related events (SREs), 
are defined as radiation to bone, pathologic fracture, surgery to bone, 
and spinal cord compression.2

Bone Metastases Destroy Bone 
Via Bone Resorption and Tumor Growth6,7

Healthy bone results from a balance of bone resorption and formation through osteoclasts and osteoblasts6
Tumor cells produce cytokines and transcription factors that promote osteoclast formation and stimulate bone resorption7
Bone resorption leads to the release of growth factors that accelerate tumor growth6

This results in a continuous cycle of bone destruction7

Bone Metastases Can Lead to Serious 
and Devastating Bone Complications8,9

Bone complications, also known as skeletal-related events (SREs), are8,9*:

Radiation to bone for bone pain and/or to prevent future bone complications

Pathologic fractures due to increased bone fragility

Spinal cord compression, potentially caused when bony metastatic deposits begin extending into the epidural space

Hypercalcemia of malignancy (serum calcium >12 mg/dL or >3.0 mmol/L)  Bone metastases can be associated with an increase in serum calcium levels, which overwhelms renal capacity to maintain calcium homeostasis

Surgery to bone to address pain or other complications (eg, surgical stabilization with fixation devices)

*Data based on a different definition of bone complications are noted throughout this presentation.

Your Patients Are Living Longer, Putting Them 
at Greater Risk for Bone Complications10-26

Bone metastases are impacting the lives of more and more patients.

  • Survival from malignancy is improving due to advances in the treatment landscape10-14
  • The estimated number of people living with bone metastases increased nearly 20% between 2008 and 201215,16

Percentage of patients with bones metastases17

Primary cancer typeIncidence of bone
metastases at autopsy
Median survival for patients with breast, prostate, and lung cancer now exceeds median time to first bone complication.18-26

Bone Complications* May Occur 
With or Without the Precursor of Pain27

  • Pain is typically the first symptom of bone metastases28
  • Pain, however, may not always be a reliable indicator of bone complications27 A retrospective analysis of patients with bone metastases from prostate cancer showed that the same percentage of patients suffered 1 or more bone complications within 2 years whether or not they had bone pain at baseline
Bone complications in patients with or without pain27
Data from the placebo arm (n=208) of a retrospective analysis evaluating the efficacy of an intravenous (IV) bisphosphonate in the reduction of bone complications and bone pain in men with bone metastases from prostate cancer.

*In this trial, bone complications or SREs were defined as pathologic fracture, surgery to bone, radiation to bone, spinal cord compression, and change in antineoplastic therapy to treat bone pain. One hundred ninety-one patients in the placebo arm had data capturing baseline pain.27

Even without pain, patients with bone metastases are at risk for bone complications.27

Patients Who Experience a Bone Complication* 
Are More Likely to Use Strong Opioids29†

  • Bone pain can be difficult to control and may respond poorly to opioid therapy9
  • Severe pain of bone metastases may become refractory to standard analgesics29
*Bone complications, also known as skeletal-related events, are defined as pathological bone fractures, the need for radiation to bone to manage pain and control local tumor burden, compression of the spinal cord, and surgery to stabilize the bone or treat an existing fracture.29
Compared with patients who do not experience bone complications.
Patients with a bone complication may experience progression of bone pain, despite standard analgesia.29

Bone Complications* Can Reduce Quality of Life4,5

Bone complications have been shown to substantially reduce quality of life in patients with certain types of advanced cancers.4,5

Subsequent bone complications may occur and further impact quality of life.4

Prior bone complications increase the risk of subsequent bone complications. Of elderlymetastatic prostate cancer patients who have experienced an initial bone complication (n=4,176),30

experienced a subsequent
bone complication

Among patients who experienced a subsequent bone complication, 55% (n=1,442) experienced a bone complication of a different type.30

* Bone complications, also known as skeletal-related events, are defined as pathologic fracture, surgery to bone, spinal cord compression, and radiation to bone.4
An analysis from the SEER Medicare–linked database (which combines clinical information from population-based cancer registries with claims information from the Medicare program), including 8,997 elderly men diagnosed with metastatic prostate cancer between 2000 and 2009 and followed through December 31, 2010 or until they were lost to follow-up (median follow-up time 18 months). Post-diagnosis bone complications were identified using claims that indicated spinal cord compression, pathologic fracture, surgery to bone, or radiation (potentially suggestive of bone palliative radiation).30

Your Patients With Bone Complications* May Experience Decreased Physical and Emotional Well-being4,5

Significant reductions in emotional, functional, and physical well-being have been observed in patients with metastatic prostate cancer and bone complications.4†
Significant reductions in emotional, functional, and physical well-being have been observed in patients with metastatic prostate cancer and bone complications.4†
Significant increases in anxiety and distress and reductions in ambulation scores were noted in patients with metastatic breast cancer and pathologic fracture.5
*Bone complications, also known as skeletal-related events, are defined as pathologic fracture, spinal cord compression with vertebral compression fracture, the need for surgery to treat or prevent pathologic fractures or spinal cord compression, or the need for radiation to bone.4
In the initial 6 months after randomization.

Bone Complications May Impose Financial and 
Personal Hardship on Patients1-5

Each type of bone complication can have a significant impact on a patient.

Radiation Has Both Proven 
Benefits and Risks to Patients

Radiation therapy can provide significant relief from pain associated with bone metastases. Patients will typically experience improvement about 2 weeks after treatment and their reduced levels of pain may last for several weeks. Beyond its palliative effect, radiation therapy may also help prevent fracture.31,32

As with any treatment, there are risks and important considerations to weigh against the benefits of radiation therapy. Therapy can be disruptive, requiring travel to daily sessions for 2 to 3 weeks.31 Additionally, patients may experience side effects (depending on location, intensity, and anatomical area of radiotherapy), such as9:

  • Gastrointestinal toxicities
  • Anorexia
  • Fatigue
  • Skin lesions
  • Bone marrow depression
  • Lung inflammation
While radiation may prove helpful, it can drain patients' time and energy.

Pathologic Fracture Can Impair Mobility and 
May Require Extensive Recovery Time

Pathologic fracture can cause serious physical limitations, including9,33:
  • Pain
  • Reduction in load-bearing capability
  • Loss of the ability to walk

If left untreated, pathological fractures rarely heal and can be painful.9,34

In a study of patients with metastatic breast cancer, return of normal ambulatory function took >1 year after pathologic fracture.5

Surgery May Bring Both Benefits and Risks to Your Patients

Choosing surgery to manage bone metastases can help relieve patients’ pain quickly and restore or preserve their ability to move. In addition, surgery that stabilizes a bone impacted by metastases, such as prophylactic surgery, can prevent future fractures.32,35

Surgery is often reserved for patients at the highest risk of suffering a painful pathologic fracture.36

While surgery may help stabilize the bone, the benefits of a procedure may be outweighed by certain risks. These risks include35-38:

  • Infection
  • Perioperative bleeding
  • Venous thromboembolism
  • Surgical failure
Patients may require extensive recovery time after surgery, with potentially no improvement in pain and functional status.39

Spinal Cord Compression Is an Oncologic Emergency33

The pain caused by spinal cord compression is exacerbated by actions as simple as sneezing or coughing.33

Your patients may also experience33,40:

  • Weakness
  • Numbness
  • Urinary retention
  • Incontinence
  • Impotence
  • Paralysis, if left untreated

The most common tumor types associated with spinal cord compression are breast, lung, and prostate.41

Spinal cord compression requires urgent evaluation and treatment.33,42

Hypercalcemia of Malignancy Can Compromise 
Patient Health and Well-being9,33,43

Hypercalcemia of malignancy, typically a result of bone destruction, can overwhelm renal capacity to maintain calcium homeostasis.9,33

Symptoms of hypercalcemia of malignancy include33:

  • Fatigue
  • Anorexia
  • Constipation
  • Deterioration of renal function
  • Worsening mental status
If hypercalcemia of malignancy is not diagnosed and treated, it can lead to arrhythmia or coma.43

Bone Complications Can Come With 
Significant Economic Burdens1-3

Retrospective observational studies have reported that costs of bone complications in patients with bone metastases from breast or prostate cancer are substantial.1-3

Inpatient $40,300–$43,000
Outpatient $11,100–$11,800
Inpatient $58,400–$64,100
Outpatient $10,700–$11,400
Inpatient $77,200–$88,800
Outpatient $4,700–$11,700
Inpatient $54,500–$102,200
Outpatient $11,900–$14,900
The average cost for a single episode of hypercalcemia of malignancy is $16,544
More than 20% of bone complications require a hospital stay for patients with bone metastases from breast, prostate, or lung cancer.1,2,40

The Impact of Bone Complications* May Extend 
to Many Aspects of Patients’ Lives4,5,40,44

  • Time away from work/home44
  • Time spent in hospitals40,44 In one study, the average hospitalization for a bone complication was 6.75 days/patient-year for lung cancer and 3.75 days/patient-year for breast cancer
  • Disruption in daily activities4,5
  • Loss of functional abilities4,5
  • Psychosocial consequences (eg, more anxiety and stress)4,5
*Bone complications, also known as skeletal-related events, are defined as pathological fracture, spinal cord compression, hypercalcemia, bone surgery or radiotherapy, or initiation of opioid analgesic use.44
Consider what the added burden of a bone complication would mean to a patient with advanced-stage cancer.

Don’t Wait, Talk to Your Patients About 
Bone Complications*

Treating the tumor is not the only concern when managing patients with cancer. Bone complications can have a devastating impact on patients and their families.1-5

When fighting advanced-stage cancer, it’s important to talk to your patients about potential consequences at the first diagnosis of a bone metastasis.

*Bone complications, also known as skeletal-related events, are defined as pathological fractures, bone instability requiring surgery to bone, radiation to bone to control local tumor burden and manage pain, and spinal cord compression.2

A Single Bone Metastasis Can Put Your 
Patients at Risk for Bone Complications8,45*

  • Bone metastases destroy bone via bone resorption and tumor growth6,7
  • As bone metastases impact more patients, so does the risk of bone complications15,16
  • Patients with bone metastases are at risk for bone complications, regardless of pain27
  • Bone complications can lead to significant physical, emotional, and financial consequences1-5
*Bone complications, also known as skeletal-related events, are defined as pathologic fracture, spinal cord compression, radiotherapy or surgery to bone, or a change in antineoplastic therapy to treat bone pain.27
Talk to your patients about bone complications at the first diagnosis of a bone metastasis.
  1. Hagiwara M, Delea TE, Saville MW, Chung K. Healthcare utilization and costs associated with skeletal-related events in prostate cancer patients with bone metastases. Prostate Cancer Prostatic Dis. 2013;16(1):23-27.
  2. Hagiwara M, Delea TE, Chung K. Healthcare costs associated with skeletal-related events in breast cancer patients with bone metastases. J Med Econ. 2014;17(3):223-230.
  3. Carter JA, Ji X, Botteman MF. Clinical, economic and humanistic burdens of skeletal-related events associated with bone metastases. Expert Rev Pharmacoecon Outcomes Res. 2013;13(4):483-496.
  4. DePuy V, Anstrom KJ, Castel LD, et al. Effects of skeletal morbidities on longitudinal patient-reported outcomes and survival in patients with metastatic prostate cancer. Support Care Cancer. 2007;15(7):869-876.
  5. Walker MS, Miller PJ, Namjoshi M, et al. Relationship between incidence of fracture and health-related qualify-of-life in metastatic breast cancer patients with bone metastases. J Med Econ. 2013;16(1):179-189.
  6. Roodman GD. Mechanisms of bone metastasis. N Engl J Med. 2004;350(16):1655-1664.
  7. Mundy GR. Metastasis to bone: causes, consequences and therapeutic opportunities. Nat Rev Cancer. 2002;2(8):584-593.
  8. Brodowicz T, O’Byrne K, Manegold C. Bone matters in lung cancer. Ann Oncol. 2012;23(9):2215-2222.
  9. Mercadante S. Malignant bone pain: pathophysiology and treatment. Pain. 1997;69(1-2):1-18.
  10. Data on file, Amgen.
  11. Schiller JH, Harrington D, Belani CP, et al; for the Eastern Cooperative Oncology Group. Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer. N Engl J Med. 2002;346(2):92-98.
  12. Ohe Y, Ohashi Y, Kubota K, et al; for the FACS Cooperative Group. Randomized phase III study of cisplatin plus irinotecan versus carboplatin plus paclitaxel, cisplatin plus gemcitabine, and cisplatin plus vinorelbine for advanced non–small-cell lung cancer: Four-arm cooperative study in Japan. Ann Oncol. 2007;18(2):317-323.
  13. Paz-Ares LG, de Marinis F, Dediu M, et al. PARAMOUNT: Final overall survival results of the phase III study of maintenance pemetrexed versus placebo immediately after induction treatment with pemetrexed plus cisplatin for advanced nonsquamous non–small-cell lung cancer. J Clin Oncol. 2013;31(23):2895-2902.
  14. Schabath MB, Thompson ZJ, Gray JE. Temporal trends in demographics and overall survival of non-small cell lung cancer patients at the Moffit Cancer Center from 1986 to 2008. Cancer Control. 2014;21(1):51-56.
  15. Hernandez RK, Adhia A, Wade SW, et al. Prevalence of bone metastases and bone-targeting agent use among solid tumor patients in the United States. Clin Epidemiol. 2015;7:335-345.
  16. Li S, Peng Y, Weinhandl ED, et al. Estimated number of prevalent cases of metastatic bone disease in the US adult population. Clin Epidemiol. 2012;4:87-93.
  17. Coleman RE. Metastatic bone disease: clinical features, pathophysiology and treatment strategies. Cancer Treat Rev. 2001;27(3):165-176.
  18. Swain SM, Kim S-B, Cortés J, et al. Pertuzumab, trastuzumab, and docetaxel for HER2-positive metastatic breast cancer (CLEOPATRA study): overall survival results from a randomised, double-blind, placebo-controlled, phase 3 study. Lancet Oncol. 2013;14(6):461-471.
  19. Miller K, Wang M, Gralow J, et al. Paclitaxel plus bevacizumab versus paclitaxel alone for metastatic breast cancer. N Engl J Med. 2007;357(26):2666-2676.
  20. Tannock IF, Fizazi K, Ivanov S, et al; for the VENICE Investigators. Aflibercept versus placebo in combination with docetaxel and prednisone for treatment of men with metastatic castration-resistant prostate cancer (VENICE): a phase 3, double-blind randomised trial. Lancet Oncol. 2013;14(8):760-768.
  21. Beer TM, Armstrong AJ, Rathkopf DE, et al; for the PREVAIL Investigators. Enzalutamide in metastatic prostate cancer before chemotherapy. N Engl J Med. 2014;371(5):424-433.
  22. Garon EB, Ciuleanu TE, Arrieta O, et al. Ramucirumab plus docetaxel versus placebo plus docetaxel for second-line treatment of stage IV non-small-cell lung cancer after disease progression on platinum-based therapy (REVEL): a multicentre, double-blind, randomised phase 3 trial. Lancet. 2014;384(9944):665-673.
  23. Sandler A, Gray R, Perry MC, et al. Paclitaxel–carboplatin alone or with bevacizumab for non–small-cell lung cancer. N Engl J Med. 2006;355(25):2542-2550.
  24. 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, placebo-controlled trials. Cancer. 2000;88(5):1082-1090.
  25. Saad F, Gleason DM, Murray R, et al; for the Zoledronic Acid Prostate Cancer Group. A randomized, placebocontrolled trial of zoledronic acid in patients with hormone-refractory metastatic prostate carcinoma. J Natl Cancer Inst. 2002;94(19):1458-1468.
  26. Rosen LS, Gordon D, Tchekmedyian NS, et al; on behalf of the Zoledronic Acid Lung Cancer and Other Solid Tumors Study Group. Long-term efficacy and safety of zoledronic acid in the treatment of skeletal metastases in patients with nonsmall cell lung carcinoma and other solid tumors: a randomized, phase III, double-blind, placebo-controlled trial. Cancer. 2004;100(12):2613-2621.
  27. Saad F, Eastham J. Zoledronic acid improves clinical outcomes when administered before onset of bone pain in patients with prostate cancer. Urology. 2010;76(5):1175-1181.
  28. Mantyh P. The science behind metastatic bone pain. Eur J Cancer. 2006;4(suppl):4-8.
  29. von Moos R, Body JJ, Egerdie B, et al. Pain and analgesic use associated with skeletal-related events in patients with advanced cancer and bone metastases. Support Care Cancer. 2016;24(3):1327-1337.
  30. Hussain A, Abdulla M, Mullins CD, et al. Prevalence of first and subsequent skeletal-related events (SREs) in U.S. elderly patients with metastatic prostate cancer (mPC). J Clin Oncol. 2014;32(suppl 15): abstract e16006.
  31. Lutz ST, Chow EL, Hartsell WF, Konski AA. A review of hypofractionated palliative radiotherapy. Cancer. 2007;109(8):1462-1470.
  32. American Cancer Society. Bone metastasis. American Cancer Society Web site. www.cancer.org/bone-metastasis-pdf. Revised February 17, 2014. Accessed February 12, 2016.
  33. Coleman RE. Clinical features of metastatic bone disease and risk of skeletal morbidity. Clin Cancer Res. 2006;12(suppl 20):6243s-6249s.
  34. Coleman RE. Management of bone metastases. Oncologist. 2000;5(6):463-470.
  35. Wedin R, Bauer HCF, Rutqvist LE. Surgical treatment for skeletal breast cancer metastases: A population-based study of 641 patients. Cancer. 2001;92(2):257-262.
  36. Ratasvuori M, Wedin R, Keller J, et al. Insight opinion to surgically treated metastatic bone disease: Scandinavian Sarcoma Group Skeletal Metastasis Registry report of 1195 operated skeletal metastasis. Surg Oncol. 2013;22(2):132-138.
  37. Weiss RJ, Tullberg E, Forsberg JA, et al. Skeletal metastases in 301 breast cancer patients: Patient survival and complications after surgery. Breast. 2014;23:286-290.
  38. Pazionis TJC, Papanastassiou ID, Maybody M, Healey JH. Embolization of hypervascular bone metastases reduces intraoperative blood loss: a case-control study. Clin Orthop Relat Res. 2014;472(10):3179-3187.
  39. Wood TJ, Racano A, Yeung H, et al. Surgical management of bone metastases: Quality of evidence and systemic review. Ann Surg Oncol. 2014;21(13):4081-4089.
  40. Lorusso V, Duran I, Garzon-Rodriguez C, et al. Health resource utilisation associated with skeletal-related events in European patients with lung cancer: A subgroup analysis from a prospective multinational study. Mol Clin Oncol. 2014;2(5):701-708.
  41. Levack P, Graham J, Collie D, et al; the Scottish Cord Compression Study Group. Don’t wait for a sensory level–listen to the symptoms: a prospective audit of the delays in diagnosis of malignant cord compression. Clin Oncol (R Coll Radiol). 2002;14(6):472-480.
  42. Katakami N, Kunikane H, Takeda K, et al. Prospective study on the incidence of bone metastasis (BM) and skeletal-related events (SREs) in patients (pts) with stage IIIB and IV lung cancer—CSP-HOR 13. J Thorac Oncol. 2014;9(2):231-238.
  43. Clines GA. Mechanisms and treatment of hypercalcemia of malignancy. Curr Opin Endocrinol Diabetes Obes. 2011;18(6):339-346.
  44. Lage M, Harrison DJ, Barber B, et al. Burden of hospitalizations associated with skeletal related events in patients with breast cancer or lung cancer and bone metastases or multiple myeloma. J Clin Oncol. 2007;25(18S[suppl 20]):17083.
  45. 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.
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