So-called prostate cancer “super responders” could live for two years or longer on immunotherapy, a major new clinical trial has revealed.
A phase II clinical trial, led globally by a team at The Institute of Cancer Research, London, UK, and The Royal Marsden Foundation Trust, found that a small number of men were alive and well after the trial had ended, and despite having had a very poor prognosis before treatment.
The researchers found that one in 20 men with end-stage prostate cancer responded to the immunotherapy pembrolizumab and the most dramatic responses was in patients whose tumours had mutations in genes involved in repairing DNA. The team is now investigating to see if this group might particularly benefit from immunotherapy.
The phase II clinical trial involved 258 men with advanced prostate cancer who had previously been treated and become resistant to androgen deprivation therapy and docetaxel chemotherapy.
The study, published in the latest edition of the Journal of Clinical Oncology, found that 5% of men treated with pembrolizumab saw their tumours shrink or disappear, while 19% had some evidence of tumour response with a decrease in prostate-specific antigen (PSA) level.
Among a group of 166 patients with particularly advanced disease and high levels of PSA, the average length of survival was 8.1 months with pembrolizumab.
Nine of these patients saw their disease disappear or partly disappear and of these, four were super-responders who remained on treatment at the end of study follow-up, with responses lasting for at least 22 months.
A second group of patients whose PSA levels were lower but whose disease had spread to the bone survived for an average of 14.1 months on pembrolizumab.
The study also compared the effectiveness of pembrolizumab in men whose tumours had the protein PD-L1 on the surface of their cancer cells and those whose tumours did not.
But researchers found that testing for PD-L1 was not sufficient to tell which patients would respond to treatment. Men with PD-L1 in their tumours survived 9.5 months compared with 7.9 months for patients without PD-L1 in their tumours.
Professor Johann de Bono, Regius Professor of Cancer Research at The Institute of Cancer Research, London, and consultant medical oncologist at The Royal Marsden NHS Foundation Trust, said: "We don’t see much activity from the immune system in prostate tumours, so many oncologists thought immunotherapy wouldn’t work for this cancer type. But our study shows that a small proportion of men with end-stage cancer do respond, and crucially that some of these men do very well indeed.
"We found that men with mutations in DNA repair genes respond especially well to immunotherapy, including two of my own patients who have now been on the drug for more than two years. I am now leading a larger-scale trial specifically for this group of patients and am excited to see the results."
Professor Paul Workman, chief executive of The Institute of Cancer Research, London, added: "Immunotherapy has had tremendous benefits for some cancer patients and it’s fantastic news that even in prostate cancer, where we don’t see much immune activity, a proportion of men are responding well to treatment.
Pembrolizumab for Treatment-Refractory Metastatic Castration-Resistant Prostate Cancer: Multicohort, Open-Label Phase II KEYNOTE-199 Study. Journal of Clinical Oncology 28 November 2019
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