Merck & Co's Keytruda shows promise with prostate cancer 'super responders'

A small proportion of men with advanced prostate cancer, who have exhausted all other treatment options, were ‘super responders’ to Merck & Co’s Keytruda (pembrolizumab) immunotherapy in a clinical trial.

UK-led researchers found that these men were alive and well even after the trial had ended, despite a very poor prognosis before treatment.

Immunotherapies were first established in skin cancer and went on to set standards in many other forms of the disease - but progress in prostate cancer has been slow with the mainstream PD-1/PD-L1 checkpoint inhibitor class drugs that dominate the market.

There is an immunotherapy approved for certain forms of prostate cancer - Valeant's Provenge (sipuleucel-T) was first developed by Dendreon and was FDA-approved in 2010, but use has not been widespread because of the logistical issues associated with cell-based therapies.

The phase 2 KEYNOTE-199 trial, led globally by a team at the Institute of Cancer Research in London and the Royal Marsden NHS Foundation Trust, involved 258 men with advanced prostate cancer receiving Keytruda who had previously been treated and become resistant to androgen deprivation therapy and docetaxel chemotherapy.

Findings published in the Journal of Clinical Oncology show that one in 20 men with end-stage prostate cancer responded to Keytruda, but although the number who benefited was small, these patients sometimes gained years of extra life.

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

Overall, 5% of men treated with Keytruda saw their tumours actually shrink or disappear, while a larger group of 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 Keytruda.

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 Keytruda.

Testing for the presence of the PD-L1 biomarker on cancer cells was not enough to predict who responded, however.

The next stage of research will involve trying to find a test that better predicts which patients will respond, with the DNA repair pathway being an obvious candidate for further investigation.