'Targeted' ovarian cancer drug could also help certain men with prostate cancer

In collaboration with the Press Association
A prostate cancer cell

Certain men with advanced prostate cancer may benefit from a drug originally developed to treat breast and ovarian cancers, according to preliminary trial results presented at a US conference.

Olaparib – developed by UK researchers – is the first cancer drug to target specific defects in cells’ ability to repair damaged DNA. It works by interfering with the activity of a protein in cancer cells called PARP.

It was licensed last December to treat women in Europe whose ovarian cancers also carry a fault in either the BRCA1 or 2 genes.

The preliminary trial findings suggest that it could be effective in treating men whose prostate tumours contain defects in genes responsible for repairing damage to DNA, including BRCA1 and 2, or another gene called ATM. 
 
In the trial, the drug halted tumour growth, lowered the number of tumour cells found in the bloodstream, and caused levels of the blood marker prostate specific antigen (PSA) to fall.
 
Of a group of 49 men with treatment-resistant, advanced prostate cancer, a third of patients (32.7 per cent, 16 men) showed a clinical response to olaparib.

But this response rate was much higher among patients whose tumours carried faults in their DNA repair machinery. 
 
Each year around 42,000 men in the UK are diagnosed with prostate cancer and 11,000 die from the disease.

If detected early, treatment including surgery, radiotherapy and hormone therapy is often highly effective. But survival is lower for men with cancer that has spread, and become resistant to hormonal drugs. For this group of men, new therapy options are urgently needed.

The Phase II trial, called TOPARP-A, was led by researchers at The Institute of Cancer Research, London (ICR) and the Royal Marsden NHS Foundation Trust.

Professor Johan de Bono, head of drug development at The ICR and TOPARP-A chief investigator, said: "Our trial shows that olaparib is effective in men with defects in DNA repair genes who do not necessarily have an inherited risk of cancer - and that we can pick up these defects in the clinic.

"This opens up the exciting possibility of delivering precise treatment for advanced prostate cancer, guided by [DNA] testing and based on the particular molecular characteristics of patients' tumours.

"The trial is also exciting because it shows that PARP inhibitors can be effective in a wider group of patients than had been thought - in men as well as women, patients with mutations in their tumours as well as those with inherited mutations, and in those with a wider range of gene defects than just BRCA mutations."

Both Cancer Research UK and  Prostate Cancer UK contributed funding to the trial. 

Professor Steve Jackson, head of Cancer Research UK's Gurdon Institute laboratories at Cambridge University, who played a leading role in the early development of olaparib, said the results were “very promising”, and highlight the potential for such drugs to treat a wider range of cancers.

"If these new results are confirmed by further patient trials, they could soon pave the way for a much-needed new treatment for late-stage prostate cancer," he said.

Dr Iain Frame, director of research at the charity Prostate Cancer UK, said: "We want to get to a stage where every man gets the treatment he needs for his specific cancer.

"We can learn so much from the successes of treatments for other cancers and we hope to see more of this to come. However, we still need to understand more about what makes prostate cancer cells tick so that we can find the right treatment at the right time for every man."

The findings were presented at the annual meeting of the American Association of Cancer Research in Philadelphia.

A second part of the trial, TOPARP-B, is now planned which will only give olaparib to men whose cancers contain detectable DNA repair faults. 

References

  • Mateo et al, DNA repair defects and antitumor activity with PARP inhibition: TOPARP, a phase II trial of olaparib in metastatic castration resistant prostate cancer, AACR conference 2015