-Patrick
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The first major clinical trial to test immunotherapy in men with advanced prostate cancer has shown promising results, albeit in a small percentage of patients.
The research was led by scientists at the Institute for Cancer Research and Royal Marsden Hospital, both in London, UK and is being presented this weekend at the American Society of Clinical Oncology Meeting in Chicago.
The trial featured 258 men treated with the immunotherapy agent pembrolizumab (marketed by Merck as Keytruda), with 38% being alive after a year and 11% who have had no cancer growth at all since the trial began.
"We were working with very late-stage patients who had progressed even after every other type of treatment. Ten to fifteen percent of men did spectacularly well," said Professor Johann de Bono, Director of the Drug Development Unit at the Institute of Cancer Research.
However what is perhaps even more interesting than the 11% of men who had substantial responses, is the researchers have reason to believe that many of these tumors may have mutations in genes which control vital cellular processes that maintain the genome, called DNA repair.
When functional, DNA repair works constantly in every cell to fix damage done to DNA, much of which occurs naturally every time the cell divides. The amount of this damage a cell endures can, however, be greatly exacerbated by external factors such as smoking, alcohol and exposure to UV light, and perhaps unsurprisingly many cancer cells have lost some of this ability to self-repair the genome.
“As with many other cancer types, many people don't benefit. We have evidence that people with DNA repair mutations do respond to the treatment, but more work is needed to confirm this," said de Bono.
This is partly underpinned by other trials showing that DNA repair deficient tumors of different types, for example, bowel cancers do respond well to immunotherapy. In addition, de Bono and colleagues will be publishing more research over the coming months which provides evidence for this link between DNA repair deficient tumors and response to pembrolizumab.
Prostate cancer can be treated in a number of ways, but some of the more extreme treatments include surgical interventions, which can cause a range of physical and psychological side effects for patients. If the patients who respond to immunotherapy can be identified, it may lead to the avoidance of these treatments for at least some men with prostate cancer.
"The drug was extremely well tolerated by our patients. If we can find out who will respond upfront, we may be able to avoid treatments such as castration for some patients," said de Bono.
All is not lost for people who don't currently respond to immunotherapy alone though. The researchers are currently running an additional clinical trial to test pembrolizumab in combination with drugs such as PARP inhibitors, which target DNA repair processes and speculatively may to some extent mimic the response to immunotherapy of those with DNA repair mutated tumors.
Prostate cancer is the third most common type of cancer in the U.S., with 164,690 men diagnosed every year. Considering the large numbers of people affected, if immunotherapy proves to be a suitable treatment for 10-15% of men with prostate cancer, it represents a significant step forward and the low toxicity gives hope that more drastic procedures may be avoidable at least for some patients if the further work to identify who will respond and who won't is successful.
"It’s exciting that immunotherapy could offer some men more time with their loved ones where they have such advanced disease that they have run out of existing treatment options," said de Bono.
FYI: from the VA research information on Veterans 
cancer drug inhibits DNA repair in cancer cells
