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High hopes for targeted prostate cancer drug

Olaparib shown to slow tumours in patients with specific DNA mutations

Mark Gould

Thursday, 29 October 2015

The first drug that targets precise genetic mutations in prostate cancer has been shown to be effective in a small trial which has been described as "significant step forward" by UK scientists.

The study,* at the Institute of Cancer Research in London, took place on 49 men with untreatable cancer.

The drug, olaparib, had low overall success, but slowed tumour growth in 88% of patients with specific DNA mutations. However, a larger clinical trial is needed before doctors can say if the drug extends life expectancy.

Cancer Research UK's Dr Aine McCarthy said the 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."

The trial results, published in the New England Journal of Medicine, showed the drug worked in 14 out of 16 men with such mutations.

Levels of Prostate Specific Antigen (PSA) produced by tumours was more than halved and there were also significant falls in the number of prostate cancer cells detected in the blood and in the size of secondary tumours.

Patients responded to the drug for between six months and nearly a year and a half. 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.

Cancer Research UK, which part funded the study, says 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.

Professor Johann de Bono, the head of drug development at the Institute of Cancer Research said: "Our trial marks a significant step forward in the treatment of prostate cancer. I hope it won't be long before we are using olaparib in the clinic to treat prostate cancer."

However, the drugs watchdog in England - the National Institute for Health and Care Excellence - has already rejected olaparib for ovarian cancer on grounds of cost - at £4,000 a month.

* Mateo J, et al. DNA-Repair Defects and Olaparib in Metastatic Prostate Cancer. N Engl J Med 2015; 373:1697-1708 October 29, 2015. DOI: 10.1056/NEJMoa1506859

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