Men with advanced prostate cancer could benefit from ‘targeted’ drug

A small UK clinical trial has found that a drug developed to target inherited gene faults could benefit some men whose prostate cancer has spread.

“This trial is exciting because it could offer a new way to treat prostate cancer by targeting genetic mistakes in cancers that have spread” – Dr Áine McCarthy, Cancer Research UK

The researchers now hope to confirm the findings in a second trial, which will test the theory of ‘precision medicine’ for prostate cancer patients further.

Olaparib (Lynparza) targets a molecule called PARP, and exploits weaknesses in the cancer cells’ ability to repair damage to their DNA.

The drug has shown promise in women with ovarian and breast cancers that carry these inherited faults. It is licensed in Europe for women with ovarian cancer who carry inherited faults in the BRCA gene, but it is not yet widely available on the NHS.

The new trial shows that some men with advanced, treatment-resistant prostate cancer also respond to the drug. Further analysis showed that the tumours of those who did respond had developed faults in genes linked with a cell’s ability to repair its DNA.

The next phase of the trial, known as TOPARP-B, will test participants’ tumours for certain faulty DNA repair genes. Those men whose tumours carry the faults will treated with olaparib.

Dr Áine McCarthy, science information officer at Cancer Research UK – which part-funded the study – said the results were “exciting”, and that the approach could offer new treatment options for men who have stopped responding to other therapies.

“This trial is exciting because it could offer a new way to treat prostate cancer by targeting genetic mistakes in cancers that have spread. The hope is that this approach could help save many more lives in the future,” she said.

The trial – published in the New England Journal of Medicine – included 49 men whose prostate cancer had stopped responding to treatment and had spread. 16 of those men responded to the drug as defined by a predetermined set of clinical measurements, including tumour growth and scans.

The research team, based at the Institute of Cancer Research in London (ICR) and The Royal Marsden NHS Foundation Trust, checked genetic data for these 16 patients and found that each carried faults in genes linked with DNA repair, potentially explaining their response to the drug.

Dr Emma Hall, study co-leader from the ICR, said the results showed how gene analysis could one day be used to match prostate cancer patients to this treatment, but stressed that results of the follow-up trial will be needed to confirm these findings.

“This phase II clinical trial combined a highly targeted cancer drug with cutting-edge genomic sequencing. We showed that a subset of men whose tumours had mutations in their DNA repair machinery responded particularly well to treatment with olaparib,” she said.

“The next trial includes only men with these mutations in their tumours, with the aim of proving that olaparib is highly effective for them,” she added.

Professor Johann de Bono, who led the study at the ICR, said he hoped the findings would lead to olaparib being used to treat men in the clinic, and that using genetic analysis in this way “becomes a standard in this and other cancers”.

The study also received funding from the Prostate Cancer Foundation, Stand Up To Cancer, Prostate Cancer UK and the Movember Foundation.