A trial of buparlisib for advanced breast cancer that is hormone receptor positive and HER2 negative (BELLE 2)

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Cancer type:

Breast cancer

Status:

Results

Phase:

Phase 3

This trial looked at a drug called buparlisib for breast cancer that had spread into tissue surrounding the breast or elsewhere in the body.

It was for women whose breast cancer:

  • had got worse despite having a hormone therapy drug called an aromatase inhibitor
  • was hormone receptor positive
  • was HER2 negative

We call breast cancer that has receptors for the hormones oestrogen and progesterone, hormone receptor positive breast cancer Open a glossary item. Breast cancer cells often have receptors for a protein called HER2. If there are only small numbers of these receptors, the cancer is called HER2 negative Open a glossary item.

More about this trial

In post menopausal Open a glossary item women, doctors often use a type of hormone therapy called aromatase inhibitors to treat advanced breast cancer. But sometimes this treatment stops working. So, doctors might use another hormone therapy called fulvestrant.

Buparlisib (BKM120) is a type of targeted cancer drug called a cancer growth blocker. It works by blocking the action of proteins called PI3K (it is a PI3K inhibitor). This stops the cancer dividing and growing.

In this trial, researchers wanted to find out if buparlisib alongside fulvestrant helps women with advanced breast cancer.

The aims of the trial were to:

  • find out if buparlisisb and fulvestrant worked better than fulvestrant on its own
  • learn more about the side effects
  • find out more about quality of life

Summary of results

The trial team found that buparlisib and fulvestrant worked better than fulvestrant on its own. But the side effects of buparlisib were quite severe so many women stopped treatment early.

Results
The researchers published the results in July 2017.

This was a phase 3 trial. 1,147 women took part. Their average age was 62. The women were put into 1 of the following groups at random, and:

  • 576 had buparlisib and fulvestrant
  • 571 had a dummy drug (placebo Open a glossary item) and fulvestrant

Neither they nor their doctor could choose which group they were in. Nor did they know which group they were in. We call this a double blind trial.

Everyone had treatment for as long as it was working and the side effects weren’t too bad.

The researchers looked at how long before the cancer started to grow again. This is called progression free survival. On average, this was:

  • 6.9 months in women who had buparlisib and fulvestrant
  • 5 months in women who had the dummy drug and fulvestrant

The researchers checked tissue samples from previous biopsies Open a glossary item the women had. They also looked at blood samples for tumour cells that had broken away from the breast cancer and were circulating in the blood (circulating tumour cells).

They wanted to see who had changes to the PI3K gene in their breast cancer cells. They found:

  • 372 women had a change to PI3K gene (had a mutation)
  • 479 women didn’t have a change to the PI3K gene (didn’t have a mutation)
  • in 296 women it wasn’t possible to tell

The researchers knew the PI3K status of 851 women. They looked at how long before the cancer started to grow again. This was on average:

  • 6.8 months in women who had buparlisib and fulvestrant
  • 4.5 months in women who had the dummy drug and fulvestrant

372 women had a PI3K gene change in their breast cancer cells. The average length of time before their cancer started to grow again was:

  • 6.8 months in women who had buparlisib and fulvestrant
  • 4 months in women who had the dummy drug and fulvestrant

Although the numbers look different for the above 2 groups, the difference wasn’t significant when tested mathematically.

Side effects
The most common serious side effects of buparlisib included:

  • changes to blood tests that show how the liver is working
  • high blood sugar levels
  • skin rash
  • mood disorders such as depression

People who had buparlisib also had more problems with:

  • loss of appetite
  • feeling or being sick
  • diarrhoea
  • sore mouth

Many women stopped treatment early. In most cases this was because of side effects. So, some didn’t have treatment, mainly buparlisib, for very long.

The results for how long women lived for overall aren’t available yet. This is because researchers are still following up some women who took part. The researchers hope to have this information towards the end of 2019.  

Conclusion
The researchers concluded that fulvestrant and buparlisib improved the length of time before the cancer started to grow again compared with fulvestrant alone. But the side effects of buparlisib were quite bad. So, they don’t plan to do more trials using this combination of treatment.

The trial team say that other drugs like buparlisib (other PI3K inhibitors), that are more selective could work better. But they need to do more trials.

This trial has increased knowledge about what works and what doesn’t for advanced breast cancer.

We have based this summary on information from the research team. 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 who did the research. 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 Andrew Wardley

Supported by

Experimental Cancer Medicine Centre (ECMC)
NIHR Clinical Research Network: Cancer
Novartis

Questions about cancer? Contact our information nurses

Freephone 0808 800 4040

Last review date

CRUK internal database number:

9940

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

Harriet wanted to try new treatments

Picture of Harriet

“I was keen to go on a clinical trial. I wanted to try new cancer treatments and hopefully help future generations.”

Last reviewed:

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