Xgeva Better Than Zometa at Reducing Risk of Breast Cancer Bone Problems

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Metastatic breast cancer is cancer that has spread to parts of the body away from the breast. In up to 80% of women diagnosed with metastatic breast cancer, the cancer spreads to one or more bones. Bone metastases are painful and can weaken bones. Doctors use the term "skeletal related event" (SRE) when talking about any of these complications related to cancer that has spread to the bones:

  • breaking a bone with metastatic cancer in it (pathologic fracture)
  • needing radiation therapy or surgery to ease bone pain or other complications from the cancer
  • spinal cord compression caused by the vertebrae (back bones) weakening or collapsing

High blood calcium (hypercalcemia) is another serious complication of bone metastases.

Zometa (chemical name: zoledronic acid) is used to strengthen bones in women diagnosed with metastatic breast cancer that has spread to the bones. Zometa also is used to lower their risk of an SRE. A study found that Xgeva (chemical name: denosumab), a new targeted therapy medicine, was better than Zometa at lengthening the time before an SRE develops. On average, women with breast cancer that has spread to the bones who got Xgeva developed the first SRE 5 months later than women treated with Zometa. These results were presented at the 2010 San Antonio Breast Cancer Symposium (SABCS).

Denosumab, branded as Prolia, is approved by the U.S. Food and Drug Administration (FDA) to treat postmenopausal women diagnosed with osteoporosis at high risk of breaking a bone or who can't take or haven't gotten any benefits from other osteoporosis treatments. In November 2010, denosumab, branded as Xgeva, was approved by the FDA to reduce the risk of SREs caused by certain cancers that have spread to bone, including breast cancer.

Targeted therapy medicines target specific aspects of cells that affect how they behave. Some targeted therapies, including denosumab, are antibodies that work like the antibodies made naturally by the body's immune system. Denosumab targets the RANK ligand (RANKL) protein that affects the activity of certain bone cells called osteoclasts. Osteoclasts cause a certain amount of bone breakdown to help regulate the body's calcium level. Osteoclasts tend to be overactive when breast cancer spreads to the bones. Overactive osteoclasts can cause bone pain and bone destruction. By blocking the RANKL protein, denosumab lowers the activity level of the osteoclasts, which reduces the risk of pain and other bone complications. Denosumab doesn't treat the cancer, only the bone complications caused by the cancer.

In this study, 2,046 women diagnosed with metastatic breast cancer that had spread to the bones were split into two groups:

  • about half the women got Xgeva every 4 weeks; Xgeva is given as an injection under the skin
  • the other women got Zometa every 4 weeks; Zometa is given intravenously

To make sure neither the doctors nor the women knew who was getting which medicine, all the women got both an injection and an intravenous infusion, one of which had no medicine in it, every 4 weeks. All the women were advised to take supplemental calcium and vitamin D during the study.

The researchers watched to see if any of the women had bone pain, bone fractures, or spinal cord compression, as well as whether any of the women needed radiation therapy or surgery to treat bone complications. They also looked to see if any of the women developed hypercalcemia.

The length of time before the first bone complication or hypercalcemia developed was 18% longer in women who got Xgeva compared to women who got Zometa. The average time it took for the first SRE or hypercalcemia to develop was about 32.4 months in women treated with Xgeva compared to 27.4 months in women treated with Zometa.

The risk of developing at least one bone complication was 15.4% lower in women who got Xgeva compared to women who got Zometa. At the time the results were analyzed, 32.9% of the women who got Xgeva had at least one SRE compared to 38.9% of the women who got Zometa.

The risk of developing more than one bone complication was 22% lower in women treated with Xgeva compared to women treated with Zometa.

Xgeva seemed to cause the same side effects as Zometa.

Both Xgeva and Zometa can cause kidney problems, but this side effect was less common in women who got Xgeva. Kidney problems developed in 5.4% of the women treated with Xgeva compared to 9.4% of the women treated with Zometa.

A rare but serious side effect of both medicines is osteonecrosis of the jaw, a condition in which the cells in the jawbone start to die. Osteonecrosis of the jaw developed in 2.5% of the women treated with Xgeva and in 1.8% of the women treated with Zometa.

About 15% of the women who got Zometa had to skip doses or receive a lower dose because of side effects, but none of the women who got Xgeva did.

Some doctors think Xgeva is a good alternative to Zometa for two reasons. Xgeva appears to work better than Zometa and is given as an injection under the skin rather than as an intravenous infusion. Still, more research is needed to fully understand Xgeva's benefits and risks for women diagnosed with metastatic breast cancer that has spread to bone.

If you've been diagnosed with metastatic breast cancer that has spread to one or more bones, you and your doctor will develop a treatment plan to minimize any pain you have and reduce your risk of bone complications. Zometa may be part of your plan, but, based on this study, you may want to ask your doctor if Xgeva might be a better alternative for you.

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