Advanced Prostate Cancer May be Cured By Immunotherapy, Trial Reveals

DNA repair mutations

“In the last few years immunotherapy has changed the way we treat many advanced cancers – but up to now, no one had demonstrated a benefit in men with prostate cancer. 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,” said Professor Johann de Bono, Director of the Drug Development Unit at the ICR, and at The Royal Marsden NHS Foundation Trust.

The team is now working on a new immunotherapy trial targeting prostate cancer patients with tumors exhibiting those mutations. One of immunotherapy’s major challenges is that there are currently no reliable tests to determine who can benefit from the treatment.

The current trial indicates that the presence of mutations in DNA repair genes may be a valuable marker of those likely to respond well. The study is a comparative analysis of the effectiveness of pembrolizumab in subjects with tumors presenting PD-L1 proteins on their surface and subjects without the protein.

PD-L2 a potential better marker

The study revealed that PD-L1 testing, unfortunately, was not sufficient to tell which patients would respond adequately to pembrolizumab but produced some evidence that testing for the PD-L2 protein could provide a better marker. If the new trial should produce similar results, it would provide hope for patients running out of options.

“Immunotherapy has proven to be a smarter, kinder treatment for many types of cancer – but it still only works for a minority of patients. The challenges we now face are how to predict in advance who will benefit, and how to make immunotherapy work for more people,” said professor Paul Workman, Chief Executive of the ICR.

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So far the trial has brought a happy ending to at least a few of its subjects. Michael English, a 72-year-old patient who was treated with pembrolizumab in 2016, said he had tried many options before with no outcome. 

“I was diagnosed with prostate cancer in 2005, and over a number of years I had hormone therapies, radiotherapy and chemotherapy, including treatment in research trials. Professor de Bono recommended pembrolizumab based on a genetic test and after only a few three-weekly cycles, we were astonished when scans showed that the tumour had become undetectable," said English.