A trial of olaparib for advanced prostate cancer that has got worse after standard treatment (TOPARP)

The researchers found that olaparib worked for men with advanced prostate cancer. It worked best for men who had certain gene changes (mutations ) in their cancer cells. It was possible to test for these gene changes so these tests could help predict who would benefit most from treatment.

About this trial
This was a phase 2 trial. 

There were 2 parts to this trial:

• TOPARP A 
• TOPARP B

TOPARP A
In this part, everyone had 400mg of olaparib twice a day. The research team looked at tumour samples (biopsies ) from the men who took part. They were looking to see if it was possible to find changes in the DNA repair genes. When this part finished then TOPARP B started. 

TOPARP B
Men were put into 1 of 2 groups at random. They had 1 of the following:

• 300mg olaparib twice a day
• 400mg olaparib twice a day

  Diagram 1

  

This part of the trial was only for men who had changes in genes that helped repair DNA. The trial team looked at tumour samples to identify these genes. Some of the genes they were looking for included the BRCA1  and BRCA 2  genes. 

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

The men had regular blood tests and scans every 3 months. The researchers followed everyone up for an average of about 25 months. They looked at the results to see how well treatment worked.

The researchers said that treatment worked if any of the following applied: 

• a decrease in the PSA level  by half (50%) compared to the level before starting treatment
• a scan that showed the tumour had shrunk by a certain amount 
• a drop in the number of circulating tumour cells in the blood – these are tumour cells that have broken away from the prostate and are circulating in the blood

These results had to be confirmed again at least 4 weeks later with another blood test or scan. 

Results
The trial team analysed the results for both parts of the trial. Their findings are summarised below.

TOPARP A
49 men joined this part of the trial. Researchers looked at how well treatment worked. They looked at tumour samples. 

They found that 16 men had tumours with changes in the DNA repair genes. 
The researchers found that, in 14 of these men, olaparib prevented cancer growth for 10 months on average. 

In the 33 men with tumours that did not have changes in DNA repair genes, olaparib worked for only 2 and prevented cancer growth for 3 months on average.

So the researchers concluded that treatment worked better in men whose tumours had faults in genes involved in repairing DNA.

TOPARP B
This part of the trial was for men with cancers that had gene changes in the DNA repair genes. Researchers tested tumour samples to check for this.

161 men had tumours with changes in 1 or more of these genes. Of those 98 were put into a group at random and had treatment.

• 49 had 300 mg olaparib
• 49 had 400 mg olaparib

They had the results for 46 men in each group. So 92 men in total. The researchers found that treatment worked for: 

• 25 out of 46 men who had 400mg of olaparib 
• 18 out of 46 men who had 300mg of olaparib

They found that olaparib stopped the cancer starting to grow again by an average of 5.5 months. They looked at how long men lived on average. This was about:

• 14 months in men who had 400mg olaparib
• 10 months in men who had 300mg of olaparib

Side effects
A few more men who had the higher dose of olaparib had side effects. The most common serious side effects of olaparib were:

• a drop in the number of red blood cells (anaemia )
• tiredness (fatigue) 

Conclusion
The trial team found that olaparib worked well for men with advanced prostate cancer who had specific changes in their cancer cells. It worked for men with:

• inherited gene faults such as BRCA1 and BRCA2
• gene changes within the cancer cells that weren’t inherited

The trial team concluded that these results support testing tumour samples for changes in the DNA repair genes. They say by testing for the gene changes before starting treatment it is possible to select men with a high chance of olaparib working.

Results from TOPARP A led to a larger trial called PROFOUND (now closed to recruitment). The trial team are continuing to look at the data collected in TOPARP B to understand more about how olaparib works. 

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 ) 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.