Bone Metastases

Bone metastases cause local disruption of normal bone remodeling, with lesions generally showing a propensity for an osteoblastic (bone-forming) phenotype on imaging. These lesions often lead to increased skeletal fractures, spinal cord compression, and severe bone pain.6  As shown in the chart below, bone metastases occur in a high proportion of cancer patients across many tumor types. Chemotherapy improves survival but has limited impact on bone metastases.2  Bone-targeted therapies do reduce skeletal-related events but have not shown an impact on survival in most cancers.3-6  Thus, bone metastases represent a clinical challenge with limited available solutions. It is estimated that 300,000 patients across all cancer indications in the United States annually have bone involvement, and metastatic bone disease represents an important unmet medical need.10

Bone metastases are prevalent in patients with castration-resistant prostate cancer (CRPC), occurring in 90% of these patients.8 Castration-resistant prostate cancer is a leading cause of cancer-related death in men in the United States and Europe,7,8 and bone metastases are the primary cause of morbidity and mortality in CRPC patients.1,9  Although most CRPC patients with bone metastases display features of both osteoblastic and osteolytic lesions, prostate cancer bone metastases are predominantly osteoblastic, with abnormal deposition of unstructured bone accompanied by increased skeletal fractures, spinal cord compression, and severe bone pain.1,9

References:

  1. Morrissey, C. & Vessella, R.I., J. Cellular Biochemistry 2007; 101(4):873-886
  2. Tannock, I.F., et. al., N. Eng. J. Med. 2004; 351:1502-1512
  3. Saad, F., et. al., J. Natl. Cancer Inst. 2004; 96:879-882
  4. Carducci, M.A., et. al., Cancer. 2007; 110:1959-1966
  5. Fizazi, K., et. al., J. Urol. 2009; 182:509-516
  6. Lipton, A., et. al., Semin. Oncol. 2010; 37(suppl 2):S15-S29
  7. SEER Cancer Statistics Review. http://www.seer.cancer.gov
  8. Ferlay, J., et. al., Eur. J. Cancer 2007; 46(4):765-781
  9. Nørgaard, M., et. al., J. Urol. 2010; 184(1):162-167
  10. Synovate Tandem Cancer Audit.  http://www.synovate.com