Current Trends in Prostate and Urothelial Cancer

Dr. Terry Friedlander discusses a few urothelial and prostate cancer treatment trends at ASCO 2018. Below is the full transcript of the interview.

Doximity: What were your thoughts when the USPSTF released the 2012 Prostate Cancer Screening Guidelines?

Friedlander: Now, those guidelines came out in response to the fact that we were over-treating prostate cancer in the years preceding that. There are very many men who had low-risk disease that probably wasn’t going to progress for the next 10 years or maybe even longer_—disease that might never kill them—_and yet we were recommending them radical surgeries and definitive radiation. These have really long-term morbidity and significant impact on sexual health, urinary health, and just sort of quality of life, and those are real real issues.

Those recommendations in 2012 said essentially don’t screen these people and we will sort of avoid all of this toxicity, you know; we’ll save all these people this significant morbidity. But again, I think there’s concern that we’re gonna under-diagnosed patients at that point.

Truthfully, a lot of the debate has centered around PSA, which is a cheap simple blood test. But we’re in an era now where we have much more informative tests in terms of genomic tests, RNA based tests, DNA based tests, that can better classify these patients.

Perhaps we shouldn’t just be making all our decisions off of PSA but rather using some of the tools we have today to make more informed decisions. I think we’re seeing now that some of the guidelines are shifting back towards being more informed about this decision-making.

Doximity: What current trends are you noticing in urothelial or prostate cancer?

Friedlander: For about thirty years, there was essentially one drug for metastatic urothelial cancer and that was Cisplatin. There are different Cisplatin-based combinations, but really it was just chemotherapy. In a sense, while chemotherapy has activity and really does help patients, it wasn’t very exciting, you know; really nothing had changed with the exception of maybe modifying regimens a little bit.

Beginning in 2016, we had the first approval of immunotherapy for prostate there for bladder cancer being atezolizumab, which is a PD-L1 checkpoint inhibitor. The reason that’s exciting is because the drug has a different mode of action, different toxicity profile, and results in long-term durable responses for some patients. That’s really exciting because these are patients who formerly had a prognosis of maybe 14 to 16 months on average, and now we have a subset of patients who were living years from the time of the diagnosis of metastatic disease and we don’t really know where that ends; some of these patients are responding for really long time. That’s really exciting, that’s a huge benefit and it’s completely changed how we talk with patients because there really is now, even in the metastatic setting, this opportunity for a long-term benefit to treatment.

That’s one development_—since that drug was approved, four other drugs, PD-1 checkpoint inhibitors, have been approved in bladder cancer. The field has sort of become wide open and now there are a number of checkpoint combination studiescheckpoint studies with chemotherapy, with other checkpoint inhibitors, with radiation, with targeted therapy—_really any combination you can think of is being tested.

That’s one development in bladder cancer that’s really exciting and there are two other, I think, really important developments and we actually heard about today at this meeting. They’re both looking at other ways to treat bladder cancer besides immunotherapy because, like I said, immunotherapy works in about 20% of patients who get it; that means 80% of metastatic bladder patients really don’t have good options short of chemotherapy.

Out of the two exciting developments, one was an antibody drug conjugate called enfortumab vedotin, so this is essentially an antibody against a protein called Nectin-4, which is expressed on a wide range of bladder cancers (most most bladder cancers expressed Nectin-4). And there is the antibody conjugated to a very toxic payload, a chemotherapy called MMAE, which sort of releases inside the cancer cell.

In the study that was just presented today, they saw about a 40% response rate and they saw responses in very poor prognosis patients_—_in patients with liver metastases who traditionally do very poorly, we saw actually evidence of good activity, I think it was a 38% response rate or so.

It’s a new option for patients that sort of functions irrespectively of their prior chemotherapy exposure and irrespectively, it seems like, of their prior immunotherapy exposure. It’s sort of adding a third line for those patients and because Nectin-4 is so widely expressed it seems like it should have activity across most patients with bladder cancer. We suddenly have an opportunity for a new treatment that really differs from the sort of traditional chemotherapy.

I should say there are some patients who have durable responses to that treatment. We don’t really know how long the longest response will be, but that that drug is now in going into phase three trials_—_it’s not yet approved, but if those phase three’s are positive, that’s going to be a new option for patients.

Doximity: How are these treatments benefiting patients?

Friedlander: There’s also an opportunity to give these agents even earlier in non-muscle days of bladder cancer in patients with BCG refractory disease who normally would be recommended to have a radical cystectomy. There’s an opportunity to give those drugs earlier and perhaps spare patients a really morbid and life-changing surgery_—_treating the disease with hopefully acceptable toxicity.

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