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Immunotherapy could extend lives of advanced prostate cancer patients

One in 20 men with advanced unresponsive prostate cancer respond to immunotherapy in clinical trial

Ingrid Torjesen

Thursday, 28 November 2019

Certain men with advanced prostate cancer who have exhausted all other treatment options could live for two years or more on immunotherapy, a clinical trial* published in Journal of Clinical Oncology suggests.

Researchers found that a small proportion of men were “super responders” and were alive and well even after the trial had ended despite having had a very poor prognosis before treatment.

The phase II clinical trial was led globally by a team at The Institute of Cancer Research, London, and The Royal Marsden Foundation Trust, and involved 258 men with advanced prostate cancer who had previously been treated and become resistant to androgen deprivation therapy and docetaxel chemotherapy.

Overall, five per cent of men treated with pembrolizumab saw their tumours actually shrink or disappear, with some gaining years of extra life. A larger group of 19 per cent had some evidence of tumour response with a decrease in prostate-specific antigen (PSA) level. The study was funded by the drug's manufacturer Merck, Sharpe & Dohme.

The most dramatic responses were seen in patients with tumours that had mutations in genes involved in repairing DNA, and the researchers are investigating whether this group might especially benefit from immunotherapy.

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 on scans. 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 lived for an average of 14.1 months on pembrolizumab.

The study 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.

Larger trials are now under way to test whether men with DNA repair gene mutations in their tumours, or those whose cancer has spread to the bone, should receive pembrolizumab as part of their care.

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: "Our study has shown that a small proportion of men with very advanced prostate cancer are super responders to immunotherapy and could live for at least two years and possibly considerably longer.

"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."

Pembrolizumab was well tolerated, with 60 per cent of patients reporting any side effects and only 15 per cent of patients experiencing grade 3-5 side effects.


*Antonarakis ES, Piulats JM, Gross-Goupil M, et al. Pembrolizumab for Treatment-Refractory Metastatic Castration-Resistant Prostate Cancer: Multicohort, Open-Label Phase II KEYNOTE-199 Study. Journal of Clinical Oncology. Published online November 27, 2019. DOI: 10.1200/JCO.19.01638

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