Denosumab-Mediated Inhibition of Bone Loss Effective in Nonmetastatic Breast Cancer Regardless of Patient Subgroup: Presented at ASCO-Breast

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Title: Denosumab-Mediated Inhibition of Bone Loss Effective in Nonmetastatic Breast Cancer Regardless of Patient Subgroup: Presented at ASCO-Breast
URL: http://www.pslgroup.com/dg/22B68A.htm
Doctor's Guide
September 8, 2008

Lisa M. Cockrell, PhD

WASHINGTON, DC -- September 8, 2008 -- Inhibition of bone loss by the investigational drug denosumab appears to be an effective treatment for aromatase inhibitor (AI)-induced osteopenia regardless of previous breast cancer treatment or risk for bone loss, according to the results a post-hoc analysis of phase 3 clinical data.

The analysis findings were presented by Devchand Paul, MD, Rocky Mountain Cancer Center, Denver, Colorado, and colleagues here on September 5 at the American Society of Clinical Oncology's Annual Breast Cancer Symposium (ASCO-Breast).

Adjuvant AI therapy has been shown to significantly prolong disease-free survival and time to recurrence in patients with nonmetastatic breast cancer. However, AI therapy is also associated with accelerated bone loss and an increased risk of fracture.

Denosumab is a fully human monoclonal antibody directed against the receptor activator of nuclear factor kappa B (RANK) ligand, an important component of osteoclast-mediated bone resorption and bone loss. The drug is under investigation for prevention of AI-induced osteopenia.

Dr. Paul and colleagues tested the efficacy and safety of denosumab in a phase 3, randomised, placebo-controlled trial of women receiving AI therapy for nonmetastatic breast cancer who had evidence of osteopenia. Patients were evaluated for bone mineral density (BMD) by dual energy X-ray absorptiometry.

After 1 year, percentage change from baseline in lumbar spine BMD increased by 5.5% in denosumab-treated patients compared with those receiving placebo (P < .0001). Significant gains in BMD continued to be evident up to 2 years. These significant increases in BMD showed that denosumab effectively inhibited bone loss during AI therapy.

The post-hoc analysis evaluated the effect of denosumab on BMD in different patient subgroups. These subgroups included those based on previous breast cancer treatment (duration of AI therapy, type of AI therapy, prior tamoxifen use), as well as those based on known risk factors for bone loss (age, time since menopause, body mass index, baseline T score).

Results showed that denosumab consistently and significantly improved BMD after 1 year of therapy regardless of patient subgroup.

Additionally, the analysis further evaluated the activity of denosumab at other skeletal sites in addition to the lumbar spine, including the hip, femoral neck, and 1/3 radius. Denosumab significantly improved BMD compared with placebo at all tested skeletal sites, again regardless of patient subgroup.

The safety profiles were similar for both the denosumab and placebo treatment groups. Although the rate of serious adverse events was higher in the denosumab arm than in the placebo arm (15% vs 9%, respectively), none were considered to be related to treatment.

According to these investigators, the positive and significant results shown both in this post-hoc analysis and in the phase 3 study support the continued evaluation of denosumab in clinical trials for the prevention and treatment of AI-induced bone loss.

[Presentation title: Subgroup Analysis of a Phase III Study of Denosumab in Women With Nonmetastatic Breast Cancer Receiving Aromatase Inhibitor (AI) Therapy. Abstract 173]

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