A trial of buparlisib and paclitaxel for advanced HER2 negative breast cancer (BELLE 4)

Cancer type:

Breast cancer
Secondary cancers




Phase 2/3
This trial looked at adding buparlisib to paclitaxel for breast cancer that is HER2 negative.  
It was women whose breast cancer had:
  • spread into tissue surrounding the breast or to another part of the body (advanced cancer)
  • low or no amounts of HER2 (HER2 negative breast cancer)

More about this trial

Breast cancer cells often have receptors for a protein called HER2 Open a glossary item. Having no or low numbers of these receptors, means the cancer is HER2 negative. 
HER2 negative breast cancer is unlikely to respond to drugs such as the trastuzumab (Herceptin). Some women might have a chemotherapy drug called paclitaxel. Researchers are looking for ways to improve treatment for women with advanced breast cancer. In this trial, they looked at adding a drug called buparlisib.  
Buparlisib (BMK120) is a type of targeted 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, some women had paclitaxel and buparlisib. And some had paclitaxel and a dummy drug (placebo).
The aims of the trial were to:
  • find out if paclitaxel and buparlisib works better than paclitaxel alone 
  • learn more about the side effects

Summary of results

The trial team found that buparlisib didn’t improve treatment when added to paclitaxel. 

The trial was open for women to join between 2012 and 2014. The researchers published the results in November 2016. 
About this trial 
This was a phase 2/3 trial. It took place worldwide. 
Women were put into treatment groups at random
416 women took part and:
  • 207 had paclitaxel and buparlisib
  • 209 had paclitaxel and a dummy drug (placebo Open a glossary item)

Before treatment, the doctors checked tumour samples the women had taken. They wanted to find out who had changes to the PI3K gene in their breast cancer cells. This is called molecular testing. 
They found:
  • 269 didn’t have a gene change in the PI3K gene 
  • 147 had a gene change (mutation Open a glossary item) in the PI3K gene 
The researchers looked at how long the women lived before the cancer started to grow again. This is called progression free survival. They didn’t find any difference:
  • between the 2 treatment groups
  • in how well treatment worked in women who had a PI3K gene change in their breast cancer cells compared to those who didn’t
So, adding buparlisib was no more help than standard paclitaxel.
Because of these findings, the trial closed earlier than planned and didn’t move into phase 3. 
Side effects
The most common side effects of paclitaxel and buparlisib included:
  • diarrhoea
  • hair loss
  • skin rash
  • feeling sick
  • high levels of sugar in the bloods
The trial team found that adding buparlisib to paclitaxel wasn’t better than paclitaxel for women with advanced HER2 negative breast cancer. But all trial results help doctors and researchers understand more about different cancers and the best way to treat them. 
Where do these results come from 
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 Iain MacPherson

Supported by

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

If you have questions about the trial please contact our cancer information nurses

Freephone 0808 800 4040

Last review date

CRUK internal database number:


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

Charlie took part in a trial to try new treatments

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“I think it’s really important that people keep signing up to these type of trials to push research forward.”

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