A trial comparing denosumab and zoledronic acid for breast cancer that has spread to the bones (20050136)

Cancer type:

Breast cancer




Phase 3

This trial compared denosumab with zoledronic acid to see which is better for breast cancer that has spread to the bones.

When cancer spreads to the bones it can make the bone weaker and more prone to fractures, and cause pain. Drugs called bisphosphonates such as zoledronic acid (Zometa) can slow down the damage and reduce pain.

Researchers hoped that another drug called denosumab  (Xgeva) may also slow down the bone damage and reduce pain. Denosumab is a type of biological therapy called a monoclonal antibody.

The aims of this trial were to

  • Find out which treatment is best at preventing problems caused by breast cancer that has spread to the bones
  • Compare the side effects of these two treatments

Summary of results

The research team found that denosumab was better than zoledronic acid for preventing bone problems in people with breast cancer that had spread to the bone.

This phase 3 trial recruited 2,046 people with breast cancer into one of two groups.

  • Group 1 had denosumab as an injection into the skin, and a dummy (placebo) drug through a drip into a vein
  • Group 2 had a dummy injection into the skin, and zoledronic acid through a drip into a vein

The people taking part were put into treatment groups by a computer. Neither they nor their doctor could decide which group they were in. This is called a randomised trial. Nor did they know which treatment they were having – so it is called a double blind randomised trial.

Everyone taking part had treatment once every 4 weeks until there were signs that their cancer started to grow again, or they became too unwell for treatment.

The research team looked at how long it was before the people taking part had bone problems or needed treatment for the cancer that had spread to their bones. This could be a fracture, radiotherapy for pain control or surgery, for example. Doctors call these ‘skeletal related events’ or SREs.

They found that the people who had denosumab had fewer skeletal related events than the people who had zoledronic acid, and had them later.

Denosumab and zoledronic acid both caused some side effects including fever, bone or joint pain and a low red blood cell count (anaemia).  Although a few more people who had zoledronic acid had side effects, the numbers were similar in each group.

Osteonecrosis of the jaw is a serious but rare side effect associated with bisphosphonates such as zoledronic acid. Just 20 out of 1,026 people in the denosumab group (2%), and 14 out of 1,020 people in the zoledronic acid group (1.4%) developed osteonecrosis of the jaw. By the time the analysis was done in 2010 this had got better in about half of those people without needing treatment. But 7 people in each group needed further treatment, such as surgery.

The research team presented further results from the trial at a conference in 2011. They looked at 652 people who took part in an extension of the trial

  • 318 people continued to have denosumab for another 2 years (meaning some people had it for 4 or 5 years altogether)
  • 334 people changed from zoledronic acid to have denosumab for 2 years

The results showed that the side effects and how long people lived were similar in both groups. A few people in each group developed osteonecrosis of the jaw, but no one taking part had any new side effects.

The research team concluded that denosumab was safe and could be a useful treatment for breast cancer that had spread to the bone.

We have based this summary on information from the team who ran the trial. The information they sent us has been reviewed by independent specialists (peer reviewed Open a glossary item) and published in a medical journal. The figures we quote above were provided by the trial team. We have not analysed the data ourselves.

Recruitment start:

Recruitment end:

How to join a clinical trial

Please note: In order to join a trial you will need to discuss it with your doctor, unless otherwise specified.

Please note - unless we state otherwise in the summary, you need to talk to your doctor about joining a trial.

Chief Investigator

Dr. Charles Brigden

Supported by

Experimental Cancer Medicine Centre (ECMC)

Freephone 0808 800 4040

Last review date

CRUK internal database number:

Oracle 884

Please note - unless we state otherwise in the summary, you need to talk to your doctor about joining a trial.

Deborah wanted to help other breast cancer patients in the future

A picture of Deborah

“Deborah agreed to take part in a trial as she was keen to help other cancer patients in the future. "If taking part in a trial means others might be helped then I’m very happy with that."

Last reviewed:

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