FDA panel rejects Denosumab for non-metastatic bone loss

[JimJimJimJim]

The FDA panel accepted evidence that Denosumab (Xvega) "prolongs bone metastasis-free survival by reducing the risk of developing bone metastases."

However, the FDA panel found that this difference in bone metastasis-free survival was modest and did not outweigh the risks of treatment, namely osteonecrosis of the jaw.

Once bone metastases are present, the current FDA approval for using Denosumab to prevent or delay bone damage remains.

Denosumab is also approved for this use in Australia, and is covered by PBS.

In one three-year trial of 1,468 prostate cancer patients with non-metastatic cancer, denosumab-treated patients had a significantly higher bone mineral density (BMD) versus placebo in the lumbar spine at two years. After three years, BMD was raised in the lumbar spine, total hip, and femoral neck, with lower incidence of new vertebral fractures than those treated with placebo.

In a second, two-year study of 252 postmenopausal breast cancer patients receiving aromatase inhibitor therapy, BMD was significantly raised in the drug treatment group versus placebo in the lumbar spine at 12 months, and in the lumbar spine, total hip, and femoral neck after two years.

Additionally, in another phase III trial, denosumab outperformed zoledronic acid in delaying skeletal-related events in prostate cancer patients with bone metastasis.

Adverse events related to treatment under this indication include arthralgia, back pain, extremity and musculoskeletal pain, hypocalcemia, and an increased risk of cataracts in prostate cancer patients.

[JimJimJimJim]

This is a study that shows the effectiveness of Denosumab in preventing bone metastases and deaths from bone metastases.

But, as the story above says, an FDA panel says that this difference in bone metastasis-free survival was modest and did not outweigh the risks of treatment, namely osteonecrosis of the jaw.

Recent Results Cancer Res. 2012;192:187-96.

Denosumab: first data and ongoing studies on the prevention of bone metastases.

von Moos R, Skacel T.

Source

Department Medical Oncology, Kantonsspital Graubuenden, Chur, Switzerland. roger.vonmoos@ksgr.ch

Abstract

Bone metastases are associated with a major patient and healthcare burden resulting from the impact and the management of associated skeletal-related events (including spinal cord compression, pathologic fracture and surgery or radiation to bone). In preclinical studies, RANK Ligand inhibition has been shown to prevent the development of bone and some visceral metastases. Clinical studies are ongoing to evaluate whether the fully human monoclonal antibody denosumab, which targets RANK Ligand, can prevent the development of bone metastases in high-risk patients. Findings from a phase 3 study in men with high-risk non-metastatic castration-resistant prostate cancer demonstrated that denosumab (120 mg every 4 weeks) significantly increased bone metastasis-free survival (primary endpoint) by 4.2 months (median) versus placebo (HR 0.85 [0.73, 0.98]; P = 0.028). This is the first study to demonstrate the clinical benefit of a bone-targeted agent in this setting. Further evaluation of denosumab in the prevention of metastatic disease is warranted and ongoing in other tumor types.

PMID: 22307376

This extract can be found on http://PubMed.com, and is in the public domain.

On PubMed.com there will be a link to the full paper (often $30, sometimes free).

Any highlighting (except the title) is not by the author, but by Jim Marshall.

Jim is not a doctor.