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Xgeva Better Than Zometa at Reducing Risk of Bone Problems in Women With Metastatic Disease

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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” 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

A high level of calcium in the blood (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 a skeletal-related event.

A study has found that Xgeva (chemical name: denosumab), a targeted therapy medicine, is better than Zometa at reducing the risk of a skeletal-related event in women diagnosed with metastatic breast cancer that has spread to the bones. The study also found Xgeva improved quality of life more than Zometa.

The research was published online on Aug. 14, 2012 by the journal Clinical Cancer Research. Read the abstract of “Bone-Related Complications and Quality of Life in Advanced Breast Cancer: Results from a Randomized Phase III Trial of Denosumab versus Zoledronic Acid.”

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 skeletal-related events 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. reported on the first results from this Xgeva study in December 2010. This new analysis confirms the earlier results as well as looking at the women’s quality of life.

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

The results:

  • 31% of the women who got Xgeva had a skeletal-related event compared to 36% of the women who got Zometa; fewer women who got Xgeva had more than one skeletal-related event
  • 12% of the women who got Xgeva needed radiation therapy compared to 16% of women who got Zometa; women who got Xgeva also went 26% longer before needing radiation compared to women who got Zometa
  • 28 women who got Xgeva developed hypercalcemia compared to 58 women who got Zometa
  • 10.4% of the women who got Xgeva developed flu-like symptoms in the first three days after treatment compared to 27.3% of women who got Zometa

Both Xgeva and Zometa can cause kidney problems, but this side effect was less common in women who got Xgeva.

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.

Xgeva also may cause severe hypocalcemia, very low blood calcium levels, which can be life-threatening. The researchers didn’t report how many, if any, women developed hypocalcemia while taking Xgeva.

To measure the women’s quality of life the researchers used a survey called FACT-G. Both treatment groups had similar quality of life scores at the beginning of the study. During the follow-up period, 34% of the women who got Xgeva had a five-point improvement in their quality of life score, compared to 31% of the women who got Zometa. Fewer women who got Xgeva had their quality of life scores get worse.

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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