A trial of buparlisib for advanced hormone receptor positive breast cancer that is HER2 negative and has got worse despite having other treatments (BELLE 3)

Cancer type:

Breast cancer

Secondary cancers

Status:

Results

Phase:

Phase 3

This trial looked at buparlisib (BKM120) for breast cancer that had spread into tissue surrounding the breast or to another part of your body.

The trial was for women who had breast cancer that had got worse despite having a type of hormone therapy called an aromatase inhibitor as well as a drug called an mTOR inhibitor.

This trial was open for women to join between 2013 and 2016. These results were published in 2018.

More about this trial

Breast cancer cells often have receptors for the hormones oestrogen or progesterone, or for a protein called HER2 Open a glossary item .

A cancer with a large number of hormone receptors is called hormone receptor positive. In post menopausal women, doctors can treat these breast cancers with hormone therapy drugs called aromatase inhibitors Open a glossary item . You might also have a targeted cancer drug . But these treatments might stop working.

Breast cancer with a small number of receptors for the HER2 protein, is called HER2 negative. Drugs such as Herceptin are unlikely to work for HER2 negative breast cancer. And researchers are looking for new treatments to help women who have this type of breast cancer.

In this trial, they looked at the drug buparlisib which is a type of targeted drug called a cancer growth blocker with a hormone drug called fulvestrant. Some people had a buparlisib and fulvestrant and others had a dummy drug (placebo) and fulvestrant.

The women who took part in this trial had breast cancer that was hormone receptor positive and HER2 negative. The cancer had spread into surrounding tissue or to another part of the body. And had got worse despite having an aromatase inhibitor and a targeted drug called an mTOR inhibitor.

The aim of this trial was to see if buparlisib and fulvestrant was better than fulvestrant only for these women.

Summary of results

Because of side effects the trial team couldn’t recommend buparlisib with fulvestrant for this group of women.

About this trial

This was a phase 3 trial. It was a randomised trial. Everyone who took part were put into 1 of 2 groups. Neither they nor their doctor chose which group they were in.

Twice as many women were put into the buparlisib and fulvestrant group than into the dummy drug (placebo Open a glossary item

) and fulvestrant group.

Of the 432 women who took part:

• 289 women were in the buparlisib and fulvestrant group

• 143 women were in the dummy drug and fulvestrant group

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Results
The team looked at the average length of time women were alive and their cancer had not got any worse. They found it was:

just under 4 months (3.9) for women in the buparlisib and fulvestrant group
just under 2 months (1.8) for women in the dummy drug and fulvestrant group

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6 months after treatment they looked at the number of women in each group who were alive and their cancer had not got any worse. They found it was:

90 women (31%) in the buparlisib and fulvestrant group
29 women (20%) in the dummy drug and fulvestrant group

While having treatment 10 women in the buparlisib and fulvestrant group died. And 6 women in the dummy drug and fulvestrant group died.

Of these 16 deaths, 14 deaths were due to the cancer. Researchers thought treatment caused the other two deaths. It was one woman in each group. In the buparlisib and fulvestrant group it was due to heart failure. In the dummy drug and fulvestrant the cause wasn’t known.

During the trial a total of 137 women died. This was:

91 women (31%) in the buparlisib and fulvestrant group
46 women (32%) in the dummy drug and fulvestrant group

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PIK3CA mutation
Researchers also looked at how well this treatment worked for women who had a gene change (mutation Open a glossary item ) called PIK3CA.

Of the 432 women, the team had this information for 348 women:

232 women in the buparlisib and fulvestrant group
116 women in the dummy drug and fulvestrant group

The team looked at the average length of time these women were alive and had no sign of cancer. They found it was significantly longer for the women in the buparlisib and fulvestrant group.

Side effects

The trial team were able to look at the side effects of 428 women:

288 women in the buparlisib and fulvestrant group
140 women in the dummy drug and fulvestrant group

A higher number of women in the buparlisib and fulvestrant group had treatment breaks due to side effects. The number in each group was:

103 women (36%) in the buparlisib and fulvestrant group
12 women (9%) in the dummy drug and fulvestrant group

A higher number of women who had buparlisib and fulvestrant group had their dose reduced due to side effects. The number in each group was:

90 women (30%) in the buparlisib and fulvestrant group
11 women (8%) in the dummy drug and fulvestrant group

A higher number of women in the buparlisib and fulvestrant group stopped treatment due to side effects. The number in each group was:

61 women (21%) in the buparlisib and fulvestrant group
7 women (5%) in the dummy drug and fulvestrant group

The most common side effects of buparlisib and fulvestrant were:

an increase of liver enzymes in the blood
a high level of sugar in the blood
feeling sick
diarrhoea
tiredness
depression

The most common side effects of the dummy drug and fulvestrant were:

an increase of liver enzymes in the blood
feeling sick
tiredness
anxiety
feeling weak
headache

Conclusion

These results do show that buparlisib with fulvestrant worked better for women with hormone receptor and HER2 positive breast cancer. However the trial team couldn’t recommend it as a treatment because of the side effects.

Even so these results do support further research into drugs like buparlisib with a hormone treatment for cancers that have the PIK3CA gene change.

Where this information comes 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.