A trial looking at rucaparib for prostate cancer that has spread (TRITON3)

Cancer type:

Prostate cancer

Secondary cancers

Status:

Results

Phase:

Phase 3

This trial compared a drug called rucaparib with standard treatment Open a glossary item for prostate cancer.

It was for men with:

prostate cancer that had spread and got worse despite having hormone treatment. This is called metastatic castration resistant prostate cancer (mCRPC).
certain gene changes (mutations ) in the prostate cancer cells

The trial was open for people to join between 2017 and 2022. The team published the results in 2023.

More about this trial

Doctors often treat metastatic prostate cancer with hormone therapy and chemotherapy. But sometimes the cancer starts to grow again.

Doctors were looking at treatments to help people in this situation. In this trial they looked at a drug called rucaparib. It is a type of targeted cancer drug Open a glossary item known as a PARP inhibitor. PARP is a protein (enzyme) found in our cells. It helps damaged cells to repair themselves.

As a cancer treatment, PARP inhibitors stop the PARP from doing its repair work in cancer cells and the cell dies.

The researchers knew that PARP inhibitors might help men whose prostate cancer cells have gene changes (mutations) including:

BRCA1
BRCA2
ATM

In this trial, 2 out of every 3 people had rucaparib. And 1 out 3 every people had standard treatment. The standard treatments were:

abiraterone – a hormone treatment
enzalutamide – a hormone treatment
docetaxel – a chemotherapy drug

The main aims of this phase 3 trial were to:

see how well rucaparib works compared to standard treatment
learn more about the side effects
see how treatment affects quality of life

Summary of results

4,855 people were considered for the trial. Only men who had one of the following genes changes could take part:

BRCA1
BRCA2
ATM

To find this out the team looked at tissue samples, blood samples or both. They found that this applied to just under one in ten people (8%). This was 405 people out of 4,855.

A total of 405 men were put into a treatment group at random:

270 had rucaparib
135 had standard treatment

The doctor decided which treatment would work best for those having standard treatment.

In the rucaparib group:

201 people had the BRCA gene change
69 people had the ATM gene change

In the standard treatment group:

101 people had the BRCA gene change
34 people had the ATM gene change

The team looked at how long before the cancer started to grow again. At 5 years this was:

10.2 months in the rucaparib group
6.4 months in the standard treatment group

14734-graph-1.png

The team also looked at how long before the cancer started to grow again in those who had a BRCA gene change. At 5 years this was:

11.2 months in the rucaparib group
6.4 months in the standard treatment group

14734-graph-2.png

They also looked at how long before the cancer started to grow again in those who had the ATM gene change. This was about:

8.1 months in the rucaparib group
6.8 months in the standard treatment group

The results for these two groups do look different. But it is more likely that the difference is due to chance, and not differences in how well the treatments worked.

Quality of life
The team looked at how treatment affected quality of life. They didn’t find much of a difference between those who had rucaparib and those who had standard treatment.

Side effects
The team say the side effects were as expected.

Most people had at least 1 side effect from treatment. But some of these were mild or didn’t last long.

Some people had more severe side effects. This was:

161 out of 270 people (60%) in the rucaparib group
69 out of 130 people (53%) in the standard treatment group

The more severe side effects of rucaparib included:

tiredness (fatigue)
a drop in the number of blood cells causing an increased risk of infection and tiredness or breathlessness

The more severe side effects of standard treatment included:

tiredness
a drop in the number of white blood cells called neutrophils causing an increased risk of infection

Conclusion
The trial team concluded that rucaparib increased the length of time before the cancer started to grow again. This was for men:

who had metastatic prostate cancer and the BRCA gene change, and
whose cancer had got worse despite hormone treatment

Rucaparib didn’t increase the length of time before the cancer started to grow again in those who had the ATM gene change.

The trial team say that testing the men’s cancer cells for these gene changes was useful. Even if they didn’t have the gene changes necessary to take part in this trial. It may have showed they were suitable for other clinical trials or targeted cancer drugs Open a glossary item . It also highlighted if someone may have had a family history of cancer.

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

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

Rucaparib or Physician’s Choice in Metastatic Prostate Cancer
K. Fizazi and others
New England Journal of Medicine, 2023 388: pages 719-732

Where this information comes from
We have based this summary on the information in the article above. This has been reviewed by independent specialists (peer reviewed Open a glossary item ) and published in a medical journal. We have not analysed the data ourselves. As far as we are aware, the link we list above is active and the article is free and available to view.