Immunotherapy Research Continues to Emerge in Urothelial Cancer

Robert Dreicer, MD

Approximately one-quarter of patients with urothelial cancer respond to immunotherapy, a number that could increase with better methods to broaden response rates and improve patient selection, explained Robert Dreicer, MD.

“The impact of immunotherapy checkpoint inhibition has been profound because there are some patients who would have [otherwise not survived], but were treated with these agents and are not only alive, but are alive and off therapy,” said Dreicer, associate director for Clinical Research and the deputy director of the University of Virginia Cancer Center. “It's a revolutionary change. Our challenge is to broaden that population.”

Currently, there are no optimal biomarkers to predict response to immunotherapy in patients with urothelial cancer. While PD-L1 expression is used, for example, patients who do not express PD-L1 can still respond to checkpoint inhibition. However, ongoing research, such as with tumor mutational burden, has the potential to overcome this challenge, Dreicer said.

In an interview with OncLive, Dreicer highlighted the current state of immunotherapy in urothelial cancer and ongoing research poised to offer more information on how to broaden its effects.

OncLive: What is the current state of immunotherapy in metastatic urothelial cancer treatment?

Dreicer: There have been significant changes in the management of advanced urothelial cancer. It's one of the solid tumors that is the most responsive to immunotherapy in the form of checkpoint inhibition. Where are we currently in terms of frontline and second-line use of these agents? What do we anticipate in terms of frontline data, meaning the trials that are testing the immunotherapy plus or minus chemotherapy to try to ascertain the optimal use? There are also challenges of finding which patients are most optimally treated with checkpoint inhibitors.

How many patients with urothelial cancer benefit from immunotherapy?

Only about 20% to 25% are truly responsive to the checkpoint inhibitors that we currently use. The challenges are identifying who is going to respond and who is not. More importantly, we need to find better ways to broaden the response rate. You can't have 1 out of 5 people responding. We need that number to go up.

What are some ways this reach can be extended?

There are novel therapeutics ongoing looking at the combinations [with PD-1 inhibitors and] CTLA-4 inhibitors. That is clearly suggestive of a broadening activity. There are other novel agents in combination. We also may find out that by adding chemotherapy to checkpoint inhibitors, we get a better response. Those are the kind of data that will be forthcoming over the next 12 to 24 months.

Where do we stand currently with biomarkers predictive of immunotherapy response?

PD-L1 expression is not helpful with deciding who might respond to checkpoint inhibitors simply because patients who don't express PD-L1 can still respond. There's been a recent FDA guidance about frontline use of single-agent checkpoint inhibitors that suggests PD-L1 expression may be useful there. Those frontline studies have yet to report, so we need to wait for more data. With tumor mutational burden and other molecular subtypes of urothelial cancer, combinations of those biomarkers may begin to give us better information about selection.

Aside from urothelial cancer, could immunotherapy have a role in prostate cancer?

We know that any solid tumor can be treated with checkpoint inhibitors, but that's only a small percent of patients with prostate cancer. At a high level, checkpoint inhibition has been a modest benefit in prostate cancer. There is a slew of trials that involve checkpoint inhibitors plus myriads of different agents in prostate cancer and we're going to need to wait and see those data. It is going to be far more complicated than it's been in other solid tumors.