Trial shows benefits of immunotherapy to prostate cancer patients

A major clinical trial has become the first to show benefits of immunotherapy in prostate cancer – for some men with advanced, otherwise untreatable disease


Professor Johann de Bono, Director of the Drug Development Unit at the Institute of Cancer Research and The Royal Marsden

An international trial, led by a team at The Institute of Cancer Research (ICR), and The Royal Marsden NHS Foundation Trust, could lead to a subset of prostate cancers joining the list of cancers that can be treated with immunotherapy.

Of the 258 men on the trial with advanced prostate cancer receiving pembrolizumab, 38% of men were still alive after a year and 11% are still receiving the treatment a year after the trial began without seeing their cancer grow.

Previous trials of immunotherapy in prostate cancer had been unsuccessful – but the latest study looked back at the genetics of the tumours, and found there are some particular groups of patients that might benefit.

Overall, only 5% of men in the trial saw their tumours actually shrink or disappear after treatment, but the proportion of responders was higher in a small group of men whose tumours had mutations to genes involved in repairing DNA.

The team at the ICR and The Royal Marsden believe that this subset of men with prostate cancer could benefit from immunotherapy, although more evidence is needed. They plan to begin a new trial of pembrolizumab.

Tumours that have mutations in specific genes involved in repairing DNA may acquire more genetic mutations as they multiply than other cancers.

Researchers at the ICR and The Royal Marsden believe that these ultra-mutant cancer cells may be particularly easy for the immune system to recognise, since they will look different from healthy cells.

The findings are in line with data from other cancer types, such as bowel cancer, where tumours with defects in DNA repair mutations are more susceptible to immunotherapy.

The study, funded by Merck Sharp & Dohme, compared the effectiveness of pembrolizumab in men whose tumours had a protein called PD-L1 on the surface of their cancer cells and those whose tumours did not. Targeting PDL-1 activity with an immune checkpoint inhibitor takes the ‘brakes’ off the immune system, setting it free to attack cancer cells.

But the study found testing for PD-L1 was not sufficient to tell which patients would respond to treatment. There was some evidence that testing for another protein called PD-L2 could be a better marker of whether men will respond, but this will need to be tested in further clinical trials.

Our study has found that immunotherapy can benefit a subset of men with advanced, otherwise untreatable prostate cancer, and these are most likely to include patients who have specific DNA repair mutations within their tumours

Professor Johann de Bono