Improved Patient Selection Needed to Optimize Expanding Options in Bladder Cancer

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.”

OncLive: What is the current state of bladder cancer?

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.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.

What combinations are looking the most promising?

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

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

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. 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.

Where is the field at currently with biomarker research?

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. 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.

What other challenges do we continue to face in the bladder cancer field?

Unfortunately, we are still not at the point now where it is beneficial for patient selection in standard practice. Maybe [we will] some day. Having conversations with patients and trying to decide what the next drug that you’re going to use is, and knowing that maybe that patient will have the opportunity to only go on one agent is challenging. Having a discussion with the patient about whether they should get platinum-based chemotherapy, depending on their level of hearing impairment or that type of thing—all those things are challenges.

Regarding treatment, what do you think the future looks like in the next 5 to 10 years?

The more that we understand about which type of bladder cancer [a patient has]—because there is not just 1 bladder cancer—and [the more we] know which type of cancer is going to respond to which treatment, [the more] we will be able to make better selections for the patients who are sitting in front of us as well as patients in general. It is so exciting to think about where we are with bladder cancer today. The fact that we have incredibly active agents in the second-line setting, and the fact that we have finally broken that barrier and been able to find agents that are suitable, active, and tolerable for patients who are not eligible for cisplatin, is in and of itself amazing.

Therefore, the idea of coming up with additional agents, how to combine them, how to sequence them, and combining immunotherapy and other targets with chemotherapy, I can just see in the future how we will have, hopefully, more effective treatments for bladder cancer and to be able to save more lives and potentially save more bladders. There is definitely a lot of work to do.