Amgen Study ID Number:

Denosumab HALT 138 Study 20040138

Study Title:
A Randomized, Double-Blind, Placebo-Controlled Study to Evaluate Denosumab in the Treatment NCT (ClinicalTrials.gov identifier):

00089674
of Bone Loss in Subjects Undergoing Androgen Deprivation Therapy (ADT) for Non-Metastatic
Prostate Cancer

Key Summary Points:

• Denosumab was associated with a 62 percent reduction in vertebral fracture at 36
FAST FACTS
months, with marked reduction evident within the first year. • The HALT 138 study evaluated
denosumab in the treatment of bone
• At 24 months, lumbar spine bone mineral density (BMD) increased by 5.6
loss in patients undergoing androgen
percent in the denosumab group compared with a 1.0 percent loss in the
deprivation therapy (ADT) for non-
placebo group.
metastatic prostate cancer
• The study was powered to measure the percentage change from baseline in lumbar • The study enrolled 1,468 non-
BMD after 24 months and the incidence of new vertebral fracture after 36 months metastatic prostate cancer patients
compared to placebo. • The trial was initiated in 2004 and
• BMD is a measure of the calcium content and strength of bones. the primary completion date was
• Physicians evaluate bone loss in patients due to osteoporosis or ADT by June 2008
measuring BMD at various sites in the body. • The HALT 138 study is the first
published study to demonstrate
• Patients were randomized in a one-to-one ratio to receive either 60 mg of denosumab
fracture reduction in men
subcutaneously every six months or placebo. All patients received daily supplemental
• No generally accepted guidelines or
calcium (1g) plus vitamin D (at least 400 IU).
FDA-approved therapies currently
• An Independent Data Monitoring Committee assessed safety on an ongoing basis. exist for the management of bone
loss due to hormone ablation therapy
Key Endpoints: in prostate cancer

Endpoints Results

• To evaluate the percentage change from baseline in • At 24 months, lumbar spine BMD increased by 5.6 percent
Endpoint
Primary

lumbar spine BMD after 24 months in the denosumab group compared with a 1.0 percent loss
in the placebo group

To assess the effect of denosumab compared with placebo

on the following:

• Patient incidence of new vertebral fractures over • Denosumab was associated with a 62 percent decrease
36 months in the cumulative incidence of new vertebral fractures at
36 months

• Patient incidence of fracture at any site over • Fewer patients in the denosumab group experienced a
Secondary
Endpoints

36 months facture at any site over 36 months, but the difference was
not statistically significant

• Time to first clinical fracture • No significant differences were observed between groups in
time to first clinical fracture

• Percentage change from baseline at month 36 in • In the denosumab group, lumbar spine BMD increased
lumbar spine BMD by 6.7 percent compared to placebo. Lumbar spine BMD
significantly increased with denosumab after month 1 and
continued to increase through month 36

(Smith MR, et al. Denosumab for the Prevention of Bone Loss and Fractures in Men Receiving Androgen Deprivation Therapy in Non-Metastatic
Prostate Cancer. N Engl J Med, 2009 Aug. 20; published online at www.nejm.org on Aug. 11, 2009.)
What is Bone Loss Due to Hormone Ablation Therapy? Amgen Study ID Number:
• Certain types of cancer treatments that stop the production of specific hormones (known
as hormone ablation therapy) may increase the risk of fractures due to bone loss. 20040138
• Many men with prostate cancer are treated with ADT as their cancer progresses.
NCT (ClinicalTrials.gov identifier):
• ADT inhibits production of testosterone, which acts as a growth factor for prostate
cancer cells; however, this treatment also leads to a decrease in bone mass, and
increases the risk of fracture (Stoch, et al., 2001) (Smith, et al., 2001). 00089674
Burden of Bone Loss Due to Hormone Ablation Therapy in Prostate Cancer
• Prostate cancer is the most common cancer in men in the United States.
• Men in the United States have a one in six chance of developing prostate cancer
within their lifetime (American Cancer Society, 2008).
• Prostate cancer is the most common form of cancer in Europe and accounts for
over 24 percent of cancer diagnoses (European Society for Medical Oncology, 2006).
• In Canada, prostate cancer is the most frequently diagnosed cancer, accounting for
26 percent of all new cancer cases (Public Health Agency of Canada, 2009).
• Prostate cancer patients undergoing ADT experience accelerated bone loss and increased
fracture risk which carry significant additional morbidity and mortality.
• For one in five men, hormone ablation therapy due to ADT results in skeletal
complications such as a fracture within five years (Shahinian, et al., 2005).
• Fractures in men receiving ADT are associated with a 39 percent decrease in
survival compared to those without a history of fracture (Oefelein, et al., 2002).
• Among men with prostate cancer who experienced a fracture, those treated with ADT were
twice as likely to be hospitalized (Shahinian, et al., 2005).
• No generally accepted guidelines or FDA-approved therapies currently exist for the
management of bone loss due to hormone ablation therapy in patients with prostate cancer.
What was the 138 Trial Patient Profile?
Inclusion:
• Patients 70 years old or older with histologically confirmed prostate cancer
• Adult patients, less than 70 years old, with histologically confirmed prostate cancer
and a history of osteoporotic fracture, or BMD T-score at the lumbar spine, total
hip, or femoral neck of less than -1
• The World Health Organization (WHO) defines a T-score of
• +1 and -1 as normal bone density
• -1 and -2.5 as low bone density or osteopenia
• -2.5 or lower is a diagnosis of osteoporosis
• Have undergone bilateral orchiectomy or initiated ADT with GnRH agonist and are
expected to continue on ADT for at least 12 months
• ECOG score of 0, 1 or 2
• These scales and criteria are used by doctors and researchers to assess
how a patient’s disease is progressing, assess how the disease affects the
daily living abilities of the patient, and determine appropriate treatment
and prognosis
Key Exclusion:
• Evidence of distant metastases
• Concurrent systematic anti-neoplastic therapy or radiotherapy, other than ADT
and/or anti-androgen therapy
• Diagnosis of any secondary non-prostate malignancy within five years of
randomization, except of adequately treated basal cell or squamous cell
skin cancer
• Current administration of oral bisphosphonates
• Administration of IV bisphosphonates within the past five years
Additional Information:
For further information, visit http://www.amgentrials.com or http://clinicaltrials.gov
Media Inquiries:
United States: Lisa Rooney, +1 (805) 447-6437
Europe/Australia: Sabeena Ahmad, +41 (0) 41 369 25 30
Canada: Sabrina Paiva, +1 (905) 285-3145