Dr Daniel George Highlights Successes of Checkpoint Inhibitors in Prostate, Bladder Cancers

Checkpoint inhibitors have begun to revolutionize bladder cancer treatments, but the benefits in prostate cancer are a little less clear at this point, explained Daniel George, MD, of the Duke Cancer Insitute.

Can you describe the progress with pembrolizumab, nivolumab, and atezolizumab in prostate and bladder cancer?
With bladder cancer, the checkpoint inhibitors, in particular PD-1 and PD-L1 inhibitors, have really begun to revolutionize this field. Already we have an accelerated approval for atezolizumab in patients previously treated with platinum agents, and most recently for platinum-ineligible patients, based largely on the response rates of 20% to as high as 30% in those populations of patients.

There's an enrichment with patients that are PD-L1 positive in their tumors or in their tumor-infiltrating lymphocytes and that's where these agents may actually be even more effective. Even in the general population we're seeing benefits associated with checkpoint inhibitors, PD-1 strategies in bladder cancer. Most recently published in the New England Journal of Medicine was the pembrolizumab study demonstrating an overall survival benefit associated with pembrolizumab over chemotherapy in patients previously treated with platinum agents.

So, clearly, this field is changing. Where that goes in the future in terms of adjuvant, neo-adjuvant, or first-line treatments remains to be seen, but there's a number of phase 3 studies going on looking at those questions.

In prostate cancer it's a little bit less clear where the PD-1 strategies and PD-L1 strategies will play out. There does seem to be some activity in patients, but it's a little bit hard to predict. It may be that combining with some of the standard of care agents, such as secondary hormonal therapies like enzalutamide or systemic radiation therapies like radium, will demonstrate some benefit. And there's some proof of concept studies going on there. There's also studies looking at it in combination with chemotherapy and with PARP inhibitors, particulary in patients who have DNA damage repair profiles in their tumors. So more to come in prostate cancer.
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