Xgeva Improves Survival Over Zometa in Advanced Lung Cancer

Patients with advanced lung cancer experienced modest improvement in survival when they received bone-targeted therapy with Xgeva® (denosumab) instead of Zometa® (zoledronic acid), according to the results of a study published in the Journal of Thoracic Oncology.

Metastatic cancer refers to cancer that has spread to distant sites in the body. Several types of cancer—including lung cancer—have a tendency to spread to the bone. Bone metastases can lead to serious problems such as fracture and spinal cord compression and may require treatment with surgery or radiation therapy. Approximately 30 to 40 percent of patients with non-small cell lung cancer (NSCLC) develop bone metastases.

Prevnenting or delaying skeletal-related events (SREs) can preserve quality of life and reduce healthcare costs. Bisphosphonate drugs such as Zometa are commonly used to reduce the risk of complications from bone metastases; however, researchers continue to explore new approaches to treatment. Xgeva is a drug that targets a protein known as the RANK ligand. This protein regulates the activity of osteoclasts (cells that break down bone). Xgeva is approved for the prevention of bone complications such as fracture in patients with bone metastases from solid (not blood-related) cancers.

A large, randomized, phase III trial compared Xgeva to Zometa for the treatment of bone metastases from solid tumors or multiple myeloma. Patients were randomized to receive subcutaneous Xgeva or intravenous Zometa. The trial included a subset of 811 patients with lung cancer—702 with NSCLC and 109 with small-cell lung cancer (SCLC).

In an analysis of all lung cancer patients, Xgeva was associated with improved median overall survival compared to Zometa—8.9 months versus 7.7 months. For patients with NSCLC who received Xgeva, the median overall survival was 9.5 months compared to 8.0 months for those who received Zometa. When the researchers further analyzed NSCLC by histological type, they found that patients with squamous cell carcinoma who received Xgeva had a median survival of 8.6 months compared to 6.4 for those who received Zometa. In the subgroup of patients with SCLC, there was a trend toward improved survival in those treated with Xgeva (5.1 months) compared to those treated with Zometa (2.5 months). The rate and severity of adverse events was similar between the two groups.

The researchers concluded that Xgeva was associated with improved overall survival compared with Zometa in patients with metastatic lung cancer.


Scagliotti GV, Hirsh V, Siena S, et al. Overall survival improvement in patients with lung cancer and bone metastases treated with denosumab versus zoledronic acid: Subgroup analysis from a randomized phase 3 study. Journal of Thoracic Oncology. 2012; 7(12): 1823-1829.

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