Bone is One of the Most Common Sites for Distant Metastases Affecting up to 75 percent of Patients with Advanced Breast Cance
THOUSAND OAKS, CA, USA | November 8, 2010 | Amgen (Nasdaq: AMGN) today announced the publication of results from a pivotal Phase 3 study of 2,046 patients which compared denosumab with Zometa(R) (zoledronic acid) in delaying or preventing skeletal-related events (SREs) in breast cancer patients with bone metastases. An SRE consists of any of the following: a pathologic fracture, the need for radiation or surgery to ameliorate bone pathology secondary to tumor growth, or spinal cord compression. The study, published today in the Journal of Clinical Oncology, found that denosumab was superior to Zometa in delaying or preventing SREs in breast cancer patients with bone metastases.
"Patients with bone metastases from cancer are at increased risk of experiencing debilitating pathologic fractures and other skeletal-related events. The results of this study show that denosumab is better than the current standard of care (Zometa) in delaying or preventing these skeletal complications for our patients with advanced breast cancer," said Alison Stopeck, M.D., associate professor of Medicine, Arizona Cancer Center, University of Arizona Health Sciences Center. "In addition to improving skeletal outcomes, denosumab has no requirement for renal monitoring and is administered as a simple subcutaneous injection."
Study Results
In the study, denosumab was superior to Zometa in delaying time to first on-study SRE (hazard ratio [HR] 0.82; 95 percent CI: 0.71-0.95; P=0.01 superiority) and time to first and subsequent (multiple) SREs (rate ratio0.77; 95 percentCI:0.66-0.89; P=0.001). Reduction in bone turnover markers was greater with denosumab.
The incidence of adverse events (AEs) (96 percent denosumab, 97 percent Zometa) and serious AEs (44 percent denosumab, 46 percent Zometa) was consistent with what has previously been reported for these two agents. AEs potentially associated with renal toxicity occurred in 4.9 percent of patients treated with denosumab compared to 8.5 percent in patients treated with Zometa.
Osteonecrosis of the jaw (ONJ) was seen infrequently in both treatment groups (20 patients receiving denosumab (2.0 percent) as compared with 14 patients (1.4 percent) receiving Zometa). There was no statistically significant difference in the rate of ONJ between the two treatment arms. Hypocalcemia occurred more frequently with denosumab. No AEs of hypocalcemia were reported as fatal, and grade 3 or 4 AEs of hypocalcemia were similar between groups (1.6 percent denosumab, 1.2 percent zoledronic acid). Overall survival (hazard ratio 0.95, 95 percent CI: 0.81, 1.11; p=0.50) and time to cancer progression (hazard ratio 0.99, 95 percent CI: 0.89, 1.11; p=0.90) was balanced between treatment arms.
Study Design
This study was an international, randomized, double-blind, double-dummy, active-controlled study, in which breast cancer patients were randomized to receive either subcutaneous denosumab 120mg and intravenous placebo (N=1,026), or Zometa administered intravenously as at least a 15 minute infusion at a dose of 4 mg (or equivalent creatinine clearance-adjusted dose in patients with baseline creatinine clearance < 60mL/min) every four weeks as per the labeled instructions. All patients were strongly recommended to take daily calcium and vitamin D supplements. The primary endpoint was time to first on-study SRE.
Bone Metastases and Skeletal Related Events (SREs): Prevalence and Impact
Bone metastases occur in more than 1.5 million patients with cancer worldwide and are most commonly associated with cancers of the prostate, lung, and breast, with incidence rates as high as 75 percent of patients with metastatic disease.(i)
Approximately 50-70 percent of cancer patients with bone metastases will experience debilitating SREs.(ii) (iii) (iv) Events considered to be SREs include fractures, spinal cord compression, and severe bone pain that may require surgery or radiation. (v) Such events can profoundly disrupt a patient’s life and can cause disability, pain or even death. (vi) (vii) (viii)
Patients who experience an SRE as a result of bone metastases incur significantly higher medical costs compared with those who do not experience such events. (ix) (x) (xi) Studies have shown that the costs of treating a SRE are significant. (x) (xii) In fact, the total economic burden of patients with bone metastases in the U.S. alone is estimated to be $12.6 billion annually.(xiii)
About Denosumab and Amgen’s Research in Bone Biology
Denosumab is the first fully human monoclonal antibody in late stage clinical development that specifically targets RANK Ligand, the essential regulator of osteoclasts (the cells that break down bone). The denosumab development program is the largest ever initiated by Amgen. This broad and deep development program demonstrates Amgen’s commitment to researching and delivering pioneering medicines to patients with unmet medical needs. Amgen is studying denosumab in numerous tumor types across the spectrum of cancer-related bone diseases. Over 11,000 patients have been enrolled in the denosumab oncology clinical trials, testing the drug for the reduction of SREs in patients with breast and prostate cancer, as well as other solid tumors and multiple myeloma, for the amelioration of treatment-induced bone loss in patients with non-metastatic breast or prostate cancers, and for its potential to delay bone metastases in prostate and breast cancers.
About Amgen
Amgen discovers, develops, manufactures and delivers innovative human therapeutics. A biotechnology pioneer since 1980, Amgen was one of the first companies to realize the new science’s promise by bringing safe and effective medicines from lab, to manufacturing plant, to patient. Amgen therapeutics have changed the practice of medicine, helping millions of people around the world in the fight against cancer, kidney disease, rheumatoid arthritis, and other serious illnesses. With a deep and broad pipeline of potential new medicines, Amgen remains committed to advancing science to dramatically improve people’s lives. To learn more about our pioneering science and our vital medicines, visit www.amgen.com.
(i) Coleman RE. Skeletal complications of malignancy. Cancer. 1997; 80(suppl): 1588-1594.
(ii) Lipton A, Theriault RL, Hortobagyi GN. Pamidronate prevents skeletal complications and is
effective palliative treatment in women with breast carcinoma and osteolytic bone metastases. Cancer 2000;88:1082-1090.
(iii) Saad F, Lipton A, Cook R, Chen YM, Smith M, Coleman R. Pathologic fractures correlated with reduced survival in patients with malignant bone disease. Cancer. 2007;110:1860-1867.
(iv) Rosen LS, Gordon D, Tchekmedyian NS, et al. Nonsmall cell lung carcinoma and other solid tumors. Cancer. 2004;100:2613-2621.
(v) Costa L, Badia X, Chow E, Lipton A, Wardley A. Impact of skeletal complications on patients’ quality of life, mobility, and functional independence. Support Care Cancer. 2008; 16: 879-889.
(vi) Norgaard M, Jensen AO, Jacobsen JB, Cetin K, Fryzek JP, Sorensen HT. Skeletal related events, bone metastasis and survival of prostate cancer: a population based cohort study in Denmark (1999 to 2007).J Urol 2010; 184:162-167.
(vii) Johnell O, Kanis JA. An estimate of the worldwide prevalence and disability associated with osteoporotic fractures. Osteoporos Int 2006;17:1726-1733.
(viii) Saad F, Gleason DM, Murray R, et al. A Randomized, Placebo-Controlled Trial of Zoledronic Acid in Patients With Hormone-Refractory Metastatic Prostate Carcinoma. Journal Ntl Cancer Inst 2002;19:1458-1468.
(ix) Delea T, Langer C, McKiernan J, et al. The cost of treatment of skeletal-related events in patients with bone metastases from lung cancer. Oncology 2004;67:390-396.
(x) Schulman KL, Kohles J. Economic burden of metastic bone disease in the U.S. American Cancer Society 2007:2334-2342.
(xi) GVD/2007:2334-2342.Barber ISPOR 2008 Poster
(xii) Lage MJ, Barber BL, Harrison DJ, Jun S. The Cost of Treating Skeletal-Related Events in Patients With Prostate Cancer. Am J Manag Care. 2008;14:317-322
(xiii) Schulman KL, Kohles J. Economic burden of metastic bone disease in the U.S. American Cancer Society 2007:2334-2342.
SOURCE Amgen
Post Views: 57
Bone is One of the Most Common Sites for Distant Metastases Affecting up to 75 percent of Patients with Advanced Breast Cance
THOUSAND OAKS, CA, USA | November 8, 2010 | Amgen (Nasdaq: AMGN) today announced the publication of results from a pivotal Phase 3 study of 2,046 patients which compared denosumab with Zometa(R) (zoledronic acid) in delaying or preventing skeletal-related events (SREs) in breast cancer patients with bone metastases. An SRE consists of any of the following: a pathologic fracture, the need for radiation or surgery to ameliorate bone pathology secondary to tumor growth, or spinal cord compression. The study, published today in the Journal of Clinical Oncology, found that denosumab was superior to Zometa in delaying or preventing SREs in breast cancer patients with bone metastases.
"Patients with bone metastases from cancer are at increased risk of experiencing debilitating pathologic fractures and other skeletal-related events. The results of this study show that denosumab is better than the current standard of care (Zometa) in delaying or preventing these skeletal complications for our patients with advanced breast cancer," said Alison Stopeck, M.D., associate professor of Medicine, Arizona Cancer Center, University of Arizona Health Sciences Center. "In addition to improving skeletal outcomes, denosumab has no requirement for renal monitoring and is administered as a simple subcutaneous injection."
Study Results
In the study, denosumab was superior to Zometa in delaying time to first on-study SRE (hazard ratio [HR] 0.82; 95 percent CI: 0.71-0.95; P=0.01 superiority) and time to first and subsequent (multiple) SREs (rate ratio0.77; 95 percentCI:0.66-0.89; P=0.001). Reduction in bone turnover markers was greater with denosumab.
The incidence of adverse events (AEs) (96 percent denosumab, 97 percent Zometa) and serious AEs (44 percent denosumab, 46 percent Zometa) was consistent with what has previously been reported for these two agents. AEs potentially associated with renal toxicity occurred in 4.9 percent of patients treated with denosumab compared to 8.5 percent in patients treated with Zometa.
Osteonecrosis of the jaw (ONJ) was seen infrequently in both treatment groups (20 patients receiving denosumab (2.0 percent) as compared with 14 patients (1.4 percent) receiving Zometa). There was no statistically significant difference in the rate of ONJ between the two treatment arms. Hypocalcemia occurred more frequently with denosumab. No AEs of hypocalcemia were reported as fatal, and grade 3 or 4 AEs of hypocalcemia were similar between groups (1.6 percent denosumab, 1.2 percent zoledronic acid). Overall survival (hazard ratio 0.95, 95 percent CI: 0.81, 1.11; p=0.50) and time to cancer progression (hazard ratio 0.99, 95 percent CI: 0.89, 1.11; p=0.90) was balanced between treatment arms.
Study Design
This study was an international, randomized, double-blind, double-dummy, active-controlled study, in which breast cancer patients were randomized to receive either subcutaneous denosumab 120mg and intravenous placebo (N=1,026), or Zometa administered intravenously as at least a 15 minute infusion at a dose of 4 mg (or equivalent creatinine clearance-adjusted dose in patients with baseline creatinine clearance < 60mL/min) every four weeks as per the labeled instructions. All patients were strongly recommended to take daily calcium and vitamin D supplements. The primary endpoint was time to first on-study SRE.
Bone Metastases and Skeletal Related Events (SREs): Prevalence and Impact
Bone metastases occur in more than 1.5 million patients with cancer worldwide and are most commonly associated with cancers of the prostate, lung, and breast, with incidence rates as high as 75 percent of patients with metastatic disease.(i)
Approximately 50-70 percent of cancer patients with bone metastases will experience debilitating SREs.(ii) (iii) (iv) Events considered to be SREs include fractures, spinal cord compression, and severe bone pain that may require surgery or radiation. (v) Such events can profoundly disrupt a patient’s life and can cause disability, pain or even death. (vi) (vii) (viii)
Patients who experience an SRE as a result of bone metastases incur significantly higher medical costs compared with those who do not experience such events. (ix) (x) (xi) Studies have shown that the costs of treating a SRE are significant. (x) (xii) In fact, the total economic burden of patients with bone metastases in the U.S. alone is estimated to be $12.6 billion annually.(xiii)
About Denosumab and Amgen’s Research in Bone Biology
Denosumab is the first fully human monoclonal antibody in late stage clinical development that specifically targets RANK Ligand, the essential regulator of osteoclasts (the cells that break down bone). The denosumab development program is the largest ever initiated by Amgen. This broad and deep development program demonstrates Amgen’s commitment to researching and delivering pioneering medicines to patients with unmet medical needs. Amgen is studying denosumab in numerous tumor types across the spectrum of cancer-related bone diseases. Over 11,000 patients have been enrolled in the denosumab oncology clinical trials, testing the drug for the reduction of SREs in patients with breast and prostate cancer, as well as other solid tumors and multiple myeloma, for the amelioration of treatment-induced bone loss in patients with non-metastatic breast or prostate cancers, and for its potential to delay bone metastases in prostate and breast cancers.
About Amgen
Amgen discovers, develops, manufactures and delivers innovative human therapeutics. A biotechnology pioneer since 1980, Amgen was one of the first companies to realize the new science’s promise by bringing safe and effective medicines from lab, to manufacturing plant, to patient. Amgen therapeutics have changed the practice of medicine, helping millions of people around the world in the fight against cancer, kidney disease, rheumatoid arthritis, and other serious illnesses. With a deep and broad pipeline of potential new medicines, Amgen remains committed to advancing science to dramatically improve people’s lives. To learn more about our pioneering science and our vital medicines, visit www.amgen.com.
(i) Coleman RE. Skeletal complications of malignancy. Cancer. 1997; 80(suppl): 1588-1594.
(ii) Lipton A, Theriault RL, Hortobagyi GN. Pamidronate prevents skeletal complications and is
effective palliative treatment in women with breast carcinoma and osteolytic bone metastases. Cancer 2000;88:1082-1090.
(iii) Saad F, Lipton A, Cook R, Chen YM, Smith M, Coleman R. Pathologic fractures correlated with reduced survival in patients with malignant bone disease. Cancer. 2007;110:1860-1867.
(iv) Rosen LS, Gordon D, Tchekmedyian NS, et al. Nonsmall cell lung carcinoma and other solid tumors. Cancer. 2004;100:2613-2621.
(v) Costa L, Badia X, Chow E, Lipton A, Wardley A. Impact of skeletal complications on patients’ quality of life, mobility, and functional independence. Support Care Cancer. 2008; 16: 879-889.
(vi) Norgaard M, Jensen AO, Jacobsen JB, Cetin K, Fryzek JP, Sorensen HT. Skeletal related events, bone metastasis and survival of prostate cancer: a population based cohort study in Denmark (1999 to 2007).J Urol 2010; 184:162-167.
(vii) Johnell O, Kanis JA. An estimate of the worldwide prevalence and disability associated with osteoporotic fractures. Osteoporos Int 2006;17:1726-1733.
(viii) Saad F, Gleason DM, Murray R, et al. A Randomized, Placebo-Controlled Trial of Zoledronic Acid in Patients With Hormone-Refractory Metastatic Prostate Carcinoma. Journal Ntl Cancer Inst 2002;19:1458-1468.
(ix) Delea T, Langer C, McKiernan J, et al. The cost of treatment of skeletal-related events in patients with bone metastases from lung cancer. Oncology 2004;67:390-396.
(x) Schulman KL, Kohles J. Economic burden of metastic bone disease in the U.S. American Cancer Society 2007:2334-2342.
(xi) GVD/2007:2334-2342.Barber ISPOR 2008 Poster
(xii) Lage MJ, Barber BL, Harrison DJ, Jun S. The Cost of Treating Skeletal-Related Events in Patients With Prostate Cancer. Am J Manag Care. 2008;14:317-322
(xiii) Schulman KL, Kohles J. Economic burden of metastic bone disease in the U.S. American Cancer Society 2007:2334-2342.
SOURCE Amgen
Post Views: 57
