FDA Approves Denosumab for the Treatment of Bone Loss in Patients With Prostate or Breast Cancer

The US Food and Drug Administration (FDA) has approved two new indications for the osteoporosis drug denosumab (Prolia), as a treatment for bone loss in men receiving androgen deprivation therapy for nonmetastatic prostate cancer and in women receiving adjuvant aromatase inhibitor therapy for breast cancer.

"Bone loss and fractures are recognized adverse effects of hormone ablation therapies but we have not had an approved treatment option to prevent these problems for our patients," said Matthew Smith, MD, PhD, director of the Genitourinary Malignancies Program at Massachusetts General Hospital Cancer Center, Boston, in a press release put out by the drugmaker, Amgen.

Denosumab was previously approved by the FDA in 2010 under the name Xgeva to help prevent skeletal-related events-including bone fractures and bone pain-in patients with cancer that has metastasized and damaged the bone.

All patients on denosumab should be adequately supplemented with calcium and vitamin D. Denosumab is contraindicated in patients with hypocalcemia. Preexistence of this condition must be corrected prior to treatment with denosumab as the condition may worsen.

The Trials

Positive results from two phase III double-blind, placebo-controlled clinical trials led to the expanded indications for denosumab. The first was a multinational 3-year study involving 1,468 men with nonmetastatic prostate cancer undergoing androgen deprivation therapy. The second was a 2-year multinational study involving 252 postmenopausal women with breast cancer receiving aromatase inhibitor therapy.

Prostate Cancer Results

In men treated with denosumab for 2 years, bone mineral density (BMD) was significantly higher at the lumbar spine (+5.6%) compared to placebo(-1.0%). Treatment difference was 6.7% (95% confidence interval [CI]: 6.2%, 7.1%); P < .0001).

After three years of treatment with denosumab, there was a  relative risk reduction of 62% (P = .0125) for incidence of new vertebral fractures-3.9% in the placebo-treated men, 1.5% for the denosumab-treated men. Differences in BMD after 3 years were 7.9% at the lumbar spine, 5.7% at the (total) hip, and 4.9% at the femoral neck.

Breast Cancer Results

In women treated with denosumab, BMD was higher at 12 months at the lumbar spine (+4.8%) compared to placebo (-0.7%), a treatment difference of 5.5% [95% CI: 4.8%, 6.3%]; P < .0001). After two years of treatment with denosumab differences in BMD were 7.6% at the lumbar spine, 4.7% at the (total) hip, and 3.6% at the femoral neck.

Adverse Events

The most common adverse reactions reported with denosumab are arthralgia and back pain. Pain in extremity and musculoskeletal pain have also been reported. In men there was a greater incidence of cataract adverse events. In women, hypercholesterolemia and cystitis were also common adverse events, and pancreatitis has also been reported.