A trial looking at denosumab for early breast cancer (D-CARE)

This trial showed that denosumab did not help stop breast cancer coming back after surgery. This was for people with high risk, early stage breast cancer.

Trial design
This trial was for people with early breast cancer that had a high risk of it coming back or spreading to the bones. Just over 4,500 people took part. 

They were put into 1 of 2 treatment groups at random: 

• half had denosumab 
• half had a dummy drug (placebo)

People had denosumab (or the placebo) as an injection under the skin. They had treatment once a month for 6 months, then once every 3 months for 4 and a half years.

Results
The research team published the main results of this trial in 2020. Everyone taking part had been on the trial for at least 5 years by then.

The team looked at how many people’s cancer had spread to their bones. They found this was just over 1 in 10 people and was similar in the 2 groups. It was:

• 292 people (13%) who had denosumab
• 305 people (14%) who had the placebo

They also looked at how many people had died. They found this was less than 1 in 10 people (9%) in each group.

In 2021 they looked in more detail at how denosumab affected the bones. When cancer spreads to the bone, it can make the bone weaker. This means people are more likely to have a bone fracture. 

The team found fewer people who had denosumab had a bone fracture, compared to those who had the placebo. And those who did, had them later. The difference was bigger for those who had denosumab and were under 50 years old or hadn’t been through the menopause yet.

More than 1 in 10 people (16%) in each group decided to stop taking part in the trial. This could have affected the trial results.

Side effects
People in both groups had side effects. These were mostly the usual side effects you’d expect from treatment for breast cancer, such as chemotherapy. Many were mild or didn’t last long. 

Denosumab can cause damage to the bones in your jaw. This is called osteonecrosis and happened in:

• 122 people (5%) in the denosumab group
• 4 people (less than 1%) in the placebo group

There is more information about the side effects of denosumab in our Cancer drugs section.

Conclusion
The trial team concluded that denosumab did not help stop breast cancer coming back or spreading to the bones in this trial. But it did help stop people having as many bone fractures. This was for people who’d had surgery for early stage breast cancer.

Sometimes trials show a treatment isn’t useful for a particular type or stage of cancer. But these trials still add to our knowledge and understanding of cancer and how to treat it.

More detailed information
There is more information about this research in the references below. 

Please note, the information we link to here is not in plain English. It has been written for healthcare professionals and researchers.

Adjuvant denosumab in early breast cancer (D-CARE): an international, multicentre, randomised, controlled, phase 3 trial
R Coleman and others
Lancet Oncology, 2020. Volume 21, pages 60-72.

Bone Health Outcomes from the International, Multicenter, Randomized, Phase 3, Placebo-Controlled D-CARE Study Assessing Adjuvant Denosumab in Early Breast Cancer
R Coleman and others
Advances in therapy, 2021. Volume 38, Issue 8, pages 4569-4580.

Where this information comes from    
We have based this summary on the information in the articles above. These have been reviewed by independent specialists (peer reviewed ) and published in medical journals. We have not analysed the data ourselves. As far as we are aware, the links we list above are active and the articles are free and available to view.