New results from a clinical trial of olaparib suggest men with a common genetic fault could prolong their life after diagnosis by taking the pill twice a day.

28 Oct 2015

Around a third of men with advanced prostate cancer could prolong their lives by taking olaparib, according to the results of a landmark Phase II clinical trial led by Professor Johann de Bono at the Institute of Cancer Research.

The drug, which is currently approved for use in women with advanced ovarian cancer, was given to 49 men who had already run the gamut of alternative treatment options. After taking the pill twice a day, over 30 per cent of the men responded to treatment in one or several of the following ways:

  • their level of Prostate Specific Antigen (PSA) in their blood dropped by 50 per cent or more;
  • the number of cancer cells circulating in their blood dropped below five per sample from an average of 37;
  • imaging scans confirmed that their tumour had stopped growing or shrunk.

Secret of drug lies in a common genetic defect

The results of the trial, published today in the New England Journal of Medicine, confirmed that olaparib works for men who have a defect in how their cells repair damaged DNA in the same way it's known to be effective for women with ovarian cancer.

This genetic defect – which can be inherited from parents or develop spontaneously – causes mistakes in the DNA to build up that can eventually lead to cancer. Olaparib prevents the cells from using a ‘back up’ DNA repair mechanism, which cancer cells rely on far more than normal cells. So blocking this mechanism causes cancer cells to build-up so much damaged DNA that it dies, while normal cells remain relatively unaffected.

In most cases, the men on the trail who responded best to olaparib were the same as the men who had a fault in one or more of the genes responsible for repairing damaged DNA. So not only might olaparib be really effective at prolonging life for around one third of men with advanced prostate cancer, but it might also be possible to pre-select the men who will respond well to this treatment by looking for a fault in their DNA repair genes. This would mean that only men who were likely to benefit from olaparib would be given it, while other men could immediately be treated with something else and not waste time taking a drug that’s unlikely to work.

First ever 'personalised medicine' trial now underway

The researchers have already started the next clinical trial of this drug, which will involve testing men for DNA damage repair faults before starting treatment and only giving olaparib to those who have the defect. This will be the first ever trial of ‘personalised medicine’ for prostate cancer. If successful, it will hopefully lead to olaparib becoming a standard treatment for men with advanced prostate cancer who have a defect in one or more of their DNA damage repair genes.

Our Director of Research, Dr Iain Frame, said: “Sometimes we find answers to research questions from unexpected sources. These results demonstrate just how much we can benefit from the success of treatments for other diseases and it’s exactly the type of research we want to see more of. Although it’s still early days, this drug has already been approved for use for other cancers, so it’s more likely it will get into the hands of the men who need it more quickly if it’s proven to be successful in further trials.”

Commenting on the fact that one of the researchers leading this work is Dr Joaquin Mateo, who is jointly funded by Prostate Cancer UK, the Movember Foundation and the Medical Research Council, Dr Frame added: “Research like this wouldn’t be possible if it wasn’t for the thousands of Mo Bros and Mo Sistas who take part in Movember every year. So with another Movember looming, it’s time to rise to the challenge so that we can take the next step forward in the fight against prostate cancer.”

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