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Improved Patient Selection Needed to Optimize Expanding Options in Bladder Cancer

Gina Columbus @ginacolumbusonc
Published: Friday, Oct 27, 2017

Jean Hoffman-Censits, MD
Jean Hoffman-Censits, MD
As the pipeline of bladder cancer continues to expand and researchers investigate targeted therapies, vaccines, antibody-drug conjugates, and checkpoint inhibitors alone and in combination, a major question that remains is which patients will achieve responses to these various agents.

Furthermore, in efforts to move beyond PD-L1 as a biomarker for response to immunotherapy, a handful of ongoing observational studies are exploring urinary biomarkers to detect urothelial carcinoma (NCT02745301, NCT02957370).

“One point is just enthusiasm and excitement for the future. Now the field is kind of constantly changing and in flux, and so just understanding the landscape is certainly one thing [to know],” said Jean Hoffman-Censits, MD. “What are the promises of combinations? Which patients should we think about using combination therapy for and which patients may just be fine and benefit from single-agent therapy? The importance and the place that platinum remains in our treatment algorithm is also important, as well as the promise of all different kinds of targeted therapy and how we might use that in the future.”

Hoffman-Censits, assistant professor, director, Multidisciplinary Genitourinary Oncology Center, Department of Medical Oncology, Jefferson University Hospital, shared her insight on the ever-changing bladder cancer field, ongoing combination trials that are showing early promise, and the unmet need of patient selection for novel therapies in an interview during the 2017 OncLive® State of the Science SummitTM on Renal Cell Carcinoma and Bladder Cancer.

OncLive: What is the current state of bladder cancer?

Hoffman-Censits: We have 2 different indications for immunotherapy. One is in the refractory state, so in patients who have metastatic urothelial cancer and have had recurrent disease within 12 months of getting cisplatin, and then whose who are not candidates for cisplatin. Both of those indications are standard-of-care indications that we give immunotherapy for. 

Of course, there are a lot of new interesting and exciting data about combinations of immunotherapy drugs put together, or immunotherapy combined with other kinds of targeted therapy. We are trying to increase the effectiveness of immunotherapy. 

What combinations are looking the most promising?

There was a lot of buzz at the 2017 ASCO Annual Meeting about the combination of pembrolizumab and IDO inhibitors, so that is exciting.

One of the other things we are all excited about is the promise of targeted therapy in bladder cancer. What we have developed with the use of immunotherapy is an entirely new population of patients who progress on or are intolerant to immunotherapy, and we need agents and pathways to treat those patients, as well. That is where the promise of some of the targeted therapies and combination therapy may lie. 

Are there additional ongoing trials in this landscape that you find intriguing?

I and others are excited about antibody-drug conjugates. One of the populations of patients that have not been as responsive to immunotherapy are those with liver metastases and other visceral metastases.

Some of the early data that we are seeing come out of those trials are showing that perhaps that is a population who will benefit from those drugs. That is heartening, and hopefully as we see more data and more of those trials get populated, perhaps they are all agents that we can use in the future. 

Where is the field at currently with biomarker research?

It would be wonderful if we had that crystal ball and we could determine who was going to respond to treatment. The other thing is not just [explore] biomarkers in terms of response to immunotherapy or targeted therapy, but let’s back it all the way up to platinum therapy. Platinum is still the most active agent that we have in urothelial cancer, and, for those patients who are candidates, they should continue to get it. We would love to have biomarkers that would better define who those patients are. We are starting to look at that in the context of prospective clinical trials.

Currently, all of the biomarker data are only limited to patients who are in clinical trials. Therefore, for physicians in clinical practice—although it’s interesting to get a tumor mutational burden or PD-L1 status for someone with urothelial cancer—you are still going to go to the second-line immunotherapy agent and then think about other kinds of therapies in a clinical trial setting from there.

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