Maybe PD-1 inhibitors have a role in advanced prostate cancer after all!


New immunotherapeutic drugs known as PD-1 inhibitors (drugs like nivolumab/Optivo and pembrolizumab/Keytruda) have shown some remarkable effects in the treatment of advanced forms of cancer like melanoma and some forms of lung cancer. However, the earliest data had seemed to suggest that these drugs had little to no effect in the treatment of advanced prostate cancer.

Surprisingly, a new paper by Graff et al. in the journal Oncotarget, has now shown that, in a small group of 10 men with advanced prostate cancer who had progressive disease after treatment with enzalutamide, all of whom were then treated with pembrolizumab along with their enzalutamide, 3/10 patients (30 percent) exhibited rapid declines in their PSA levels, down to around 0.1 ng/ml. (For more information, see also this commentary on the ScienceDaily web site.)

The three men who responded so well to PD-1 treatment had started with serum PSA levels of 46, 71, and 2,503 ng/ml after treatment with enzalutamide. These PSA levels plummeted to < 0.1 ng/ml after treatment, and the three patients were progression-free at 30, 55, and 16 weeks of follow-up, respectively.

The research team is clearly now focused on whether they are able to identify and characterize a specific subset of men who, based on their tumor genetics or other biological factors, may be highly responsive to treatment with a PD-1 inhibitor. It may take a while to accurately define and characterize such a subset of men, but this clearly raises the hope that there could indeed be a definable group of men with metastatic and/or castration-resistant prostate cancer who are good candidates for treatment with at least one of the new PD-1 inhibitors.

We should be clear that this is a set of very early results from this Phase II clinical trial, and that (as yet) there is no evidence that such treatment has been able to lead to an overall or a prostate cancer-specific survival benefit in a definable set of patients.

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