A trial looking at hormone therapy with other treatments for prostate cancer (STAMPEDE trial results)

Cancer type:

Prostate cancer

Secondary cancers

Status:

Results

Phase:

Phase 3

This is a summary of the results of the STAMPEDE trial that the team have published so far.

The study included men who:

had a high risk of the cancer spreading or prostate cancer that has already spread to the lymph nodes or elsewhere in the body
were starting long term hormone therapy for the first time
were fit enough to have chemotherapy

Cancer Research UK supported this trial.

More about this trial

One of the usual treatments for prostate cancer that has spread outside the prostate gland or has a risk of spreading is hormone therapy. This blocks or lowers the amount of testosterone Open a glossary item

in the body. It can work very well, but the cancer often starts to grow again at some stage. Doctors think that having other treatments at the same time as hormone therapy may work better than hormone therapy alone.

In this trial, everybody had standard hormone therapy as usual. And some had other treatments as well.

These treatments were:

a drug called zoledronic acid
a chemotherapy drug called docetaxel
an anti inflammatory drug called celecoxib
another type of hormone therapy called abiraterone
radiotherapy to the prostate
another type of hormone therapy called enzalutamide
a drug called metformin
a hormone patch called transdermal oestradiol

The aim of this trial was to see if adding these treatments to hormone therapy improves treatment for prostate cancer.

Summary of results

The trial team have published some results for the STAMPEDE trial. In summary, the main findings are:

adding docetaxel to hormone therapy improves the length of time men live – this is called overall survival
adding abiraterone to hormone therapy improves overall survival and delays the time until the cancer gets worse
adding radiotherapy to hormone therapy in men with less prostate cancer spread improves overall survival
celecoxib doesn’t help men live longer
adding abiraterone to hormone therapy and radiotherapy could be a new standard treatment option for some men. These are men whose prostate cancer hasn’t spread to another part of the body.

There is a detailed summary of each published result below.

About this trial

This was a phase 3 trial. There were a number of different treatment groups in this trial. It compared usual hormone therapy with usual hormone therapy and one or more other treatments.

Usual hormone therapy might include:

injections or implants to stop the testicles making testosterone or to block the effects of testosterone
surgery to remove the testicles or the parts of the testicles that make testosterone - this is called an orchidectomy

Men having injections or implants had them for at least 2 years.

Most of the groups have results. We plan to add the results of the other groups when they become available.

Those taking part were put into a treatment group at random:

Group A had hormone therapy - this group doesn't have results yet

Group K had hormone therapy and metformin -this group doesn't have results yet

Group L had the transdermal oestradiol patch - this group doesn't have results yet

Group B had hormone therapy and zoledronic acid - this group has results

Group C had hormone therapy and docetaxel - this group has results

Group D had hormone therapy and celecoxib - this group has results

Group E had hormone therapy, zoledronic acid and docetaxel - this group has results

Group F had hormone therapy, zoledronic acid and celecoxib - this group has results

Group G had hormone therapy and abiraterone - this group has results

Group H had hormone therapy and radiotherapy to the prostate - this group has results

Group J had hormone therapy, abiraterone and enzalutamide - this group has results

Results for hormone therapy alongside docetaxel, zoledronic acid or both (Group B, group C and group E)

Men joined this part of the trial between 2005 and 2011. These results were published in 2016.

2,962 men took part. They were put into treatment groups at random:

1,184 had hormone therapy
593 had hormone therapy and zoledronic acid
592 had hormone therapy and docetaxel
593 had hormone therapy, zoledronic acid and docetaxel

Some men, whose cancer hadn’t spread to lymph nodes or elsewhere in the body also had radiotherapy.

stampede-results-randomisation.png

The researchers looked at how well treatment worked. To do this, they looked at how long men lived. This is called overall survival.

On average, this was:

71 months in men who had hormone therapy
81 months in men who had hormone therapy and docetaxel
76 months in men who had hormone therapy, zoledronic acid and docetaxel

So, men who had docetaxel alongside hormone therapy lived on average 10 months longer than men who had hormone therapy alone. But having zoledronic acid didn’t improve overall survival.

Side effects

Men having docetaxel had more side effects. The most common were:

an increased risk of infection with a fever
an increased risk of infection

Over half of the men who had docetaxel had a serious side effect. 8 men who had docetaxel died from serious infections.

Results for men who had hormone therapy and abiraterone (Group G)

Men joined this part of the trial between 2011 and 2014. The researchers published these results in 2017.

1,917 men took part. They were put into treatment groups at random:

957 had hormone therapy
960 had hormone therapy, abiraterone and the steroid drug prednisolone

Men whose cancer hadn’t spread to lymph nodes or elsewhere in the body also had radiotherapy.

stampede-results-randomisation-2.png

The researchers looked at how well treatment worked. To do this, they looked at the number of men living at 3 years.

This was about:

7 out 10 men (76%) who had hormone therapy (group 1)
8 out of 10 men (83%) who had hormone therapy and abiraterone (group 2)

STAMPEDE results bar graph 1

They also looked at whose cancer got worse. This happened in:

535 men who had hormone therapy
248 men who had hormone therapy and abiraterone

So, having abiraterone alongside hormone therapy reduces the chances of the cancer spreading or coming back.

Side effects

Men who had abiraterone had worse side effects. The most common were:

changes in some blood test results
high blood pressure
breathing problems

Hormone therapy can cause bone problems. But the trial found that abiraterone reduced the risk of serious bone problems by a half.

Results for hormone therapy and celecoxib, some men also had zoledronic acid (Group D and group F)

Men joined this part of the trial between 2005 and 2011. Researchers published these results in 2017.

1,245 men joined this part of the trial. Of those:

622 had hormone therapy
312 had hormone therapy and celecoxib
311 had hormone therapy, celecoxib and zoledronic acid

The researchers did an early analysis of the results in 2012. They looked at how long men lived. This is called overall survival. These results did not show clearly that adding celecoxib with or without zoledronic acid improved overall survival for these men.

So, these parts of the trials closed early and no more men took part.

Results for hormone therapy and radiotherapy to the prostate (Group H)

Men joined this part of the trial between 2013 and 2016. They all had cancer that had spread elsewhere in the body (metastatic cancer). Researchers published these results in 2018.

2,061 men took part. They were put into treatment groups at random:

1,029 had hormone therapy
1,032 had hormone therapy and radiotherapy

Some men also had docetaxel.

stampede-results-randomisation-3.png

The researchers looked at how long men lived. To do this, they followed the men for a period of 3 years. The researchers found that on average, there was no difference in how long men in the 2 groups lived. So, adding radiotherapy to hormone therapy didn’t improve overall survival.

But they found that radiotherapy helped a specific group of men. The trial team looked at how far the cancer had spread.

In:

819 men, the cancer had spread a little bit. This is called low metastatic burden. This means it hadn’t spread beyond lymph nodes and/or nearby bones
1,120 men, the cancer had spread further – this is called a high metastatic burden
122 men the trial team didn’t have this information

At 3 years, researchers looked at the number of men living whose cancer had spread a little bit. This was about:

8 out of 10 (81%) men who had hormone therapy and radiotherapy (group 1)
7 out of 10 (73%) men who had hormone therapy (group 2)

Radiotherapy to the prostate gland also delayed the cancer getting worse. So, having radiotherapy with hormone therapy helped men who had a little cancer spread to live longer.

STAMPEDE results bar graph 2

But they found that radiotherapy didn’t help men live longer if their cancer had spread further at the time of diagnosis.

Side effects

Men who had radiotherapy had more problems with their bladder or bowel. For example, problems passing urine or diarrhoea. These were expected side effects.

Results for trial group G and trial group J
Researchers published these results in 2021. Most of the men had newly diagnosed cancer.

These results looked at men who had prostate cancer that:

hadn’t spread to another part of the body and
had a high risk of the cancer spreading

The team analysed the information for 1,974 men. Of those:

988 men had hormone therapy alone (group A)
986 men had hormone therapy and abiraterone. Some also had enzalutamide (groups G and J)

In group G:

455 men had hormone therapy (control group A)
459 men had hormone therapy, abiraterone and the steroid drug prednisolone

STAMPEDE results Group G randomisation diagram

In group J:

533 men had hormone therapy (control group A)
527 men had hormone therapy, abiraterone, prednisolone and enzalutamide. This is combination treatment.

STAMPEDE results Group J randomisation diagram

The team followed everyone for about 6 years. They looked at how well treatment worked. To do this they looked at the number of people who had died or whose cancer had spread to another part of the body. At 6 years they found this happened in:

306 men who had hormone therapy alone
180 men who had hormone therapy and abiraterone, with or without enzalutamide

STAMPEDE results bar graph showing how well treatment worked after 6 years

They also looked at the number of men living at 6 years. They found this was:

just under 8 out of 10 men (77%) who had hormone therapy
just under 9 out of 10 men (86%) who had hormone therapy and abiraterone

STAMPEDE results bar graph showing percentage of men living at 6 years

The team concluded that adding abiraterone to hormone therapy improved outcomes for people. Adding enzalutamide to abiraterone didn’t work any better and the side effects were worse. The team say that abiraterone and prednisolone could be a new standard treatment option for this group of men.

Side effects
Men who had abiraterone had more problems with high blood pressure and mild liver changes. Those who had enzalutamide had more severe problems with high blood pressure, problems getting an erection, tiredness and liver changes.

Main conclusions of the STAMPEDE trial so far

The researchers found that some of the treatments they added to hormone therapy improved overall survival for men whose prostate cancer had spread or had a high risk of spread. These included:

docetaxel
abiraterone which also reduces the chances of the cancer spreading or coming back
radiotherapy in men with less prostate cancer spread (low metastatic burden)
abiraterone and prednisolone for men whose cancer hadn’t spread to another part of the body

The treatments they added to hormone therapy that didn’t improve overall survival included:

celecoxib
zoledronic acid and adding it to docetaxel didn’t add any extra benefit to having docetaxel and hormone therapy
adding enzalutamide to abiraterone

The results of the STAMPEDE trial have changed the standard of care for men with prostate cancer.

Further results

The trial team are continuing to follow up all the men who are taking part in STAMPEDE. They want to find out more about the long term side effects of treatment.

We plan to update this summary when more results become available.

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.