Dr. Benjamin Miron on Treatment Patterns and Outcomes Among Patients with Metastatic Bladder Cancer

By Robert Dillard - Last Updated: July 15, 2021

GU Oncology Now spoke with Dr. Benjamin Miron, an oncology follow at Fox Chase Cancer Center to discuss a study which was presented at this year’s ASCO meeting titled “Real-world treatment patterns and clinical outcomes among patients with metastatic
urothelial carcinoma.”

GU Oncology Now: Can you give us some background on yourself?

Dr. Benjamin Miron: Sure. I’m a medical oncology fellow at Fox Chase Cancer Center. I’m interested in GU oncology and that’s been my research focus. And I was fortunate enough to be able to work on this project with a few other really talented people at Fox Chase, which was published at ASCO this year.

What prompted you and your team to undertake this study?

So the impetus for this study was really that the field of bladder cancer has really changed over the last five years or so. Specifically, we now have immunotherapies which have been approved in the metastatic setting, and the emergence of these checkpoint inhibitors, the PD-1 and PD-L1 inhibitors, have really become a part of the treatment for most patients. And we also have some other active agents in the second-line setting. And so, although our field has really changed a lot, these advances have changed therapy mostly in the second-line setting and beyond, and also the maintenance setting because platinum-based chemotherapy is still the standard of care for patients who are eligible to receive it first.

So knowing that, we wanted to look at how these new agents being approved, specifically immunotherapies, might influence how we think about platinum-based chemotherapy. In platinum-based chemotherapy, we have information about the difference between the agents that we use, and the backbone of the regimens that we use is usually cisplatin or carboplatin. And we have randomized data that suggests that has platinum superior carboplatinum. Carboplatin is a modified version of cisplatin. And because of those modifications, that affects how it binds DNA and also its toxicity. So the data that we have previously shows that cisplatin is superior, and that’s both for response rates and overall survival, but we really wanted to know if that difference between cisplatin and carboplatin holds to be clinically meaningful now that we have more effective second line therapies, which we really didn’t have when those studies were done.

How was the study conducted and what were the findings?

Okay, sure. So this is an observational retrospective cohort study using… It was really powered by the flatter and health database, which is, it’s a database that’s curated from electronic medical records and it’s quite large and has a large proportion of bladder cancer patients. And it really allowed us to ask this question effectively. And so, what we did is we looked at, we really limited our study of this database to the time period where immunotherapy was approved in the second line setting. And then, we looked at patients who got first-line chemotherapy, either with gemcitabine cisplatin or gemcitabine carboplatin, and then went on to get immunotherapy. And we define that immmunotherapy as a single agent treatment with a variety of PD-1, PD-L1 inhibitors that are approved.

Did any of the study’s findings surprise you?

I would say that they did. I think the field in general has felt that cisplatin is superior, but there are some limitations to its use based on its toxicity. I think that one of the surprising findings potentially was that a larger portion than we might expect of patients who, technically based on our rough estimation of cisplatin ineligibility, actually receive carboplatin. And the main findings from the study were really that when we looked at overall survival from the start of first-line therapy followed by immunotherapy, we didn’t see a meaningful difference in overall survival based on the first-line chemotherapy regimen that these patients received. So it didn’t necessarily surprise us, but it was really informative.

What limitations did the study have?

So yeah, I think the main limitations of the study is that it’s really, it’s a retrospective study. There are some biases that are introduced always when you’re doing these types of studies. I think one specific potential limitation of this study that’s beyond that methodology, is that because we were looking at patients who got first-line chemotherapy, and then also got second-line immunotherapy, that means that they required a second-line treatment. We do know that there’s a small population of patients who get a first-line cisplatin who have really durable responses. So if we take that into consideration, we may have not captured that and how that may bias the results in some way. But we’re working on trying to estimate that with this dataset for the publication that we’re working on now.

What are the overall clinical implications of these findings?

I think because of a methodology that we just discussed, that it’s a retrospective study, I don’t think it’s necessarily practice changing. But I think that it does give us some kind of numerical approximation of what the magnitude differences between these two drugs, if these patients are able to go on to get second-line treatment. And I think now we have a combination of clinical trial data, which is a little bit older, and some other clinical trials that the control arms of clinical trials that were done more recently, we have this real-world data that in conjunction with clinical experience really gives us more comprehensive data set to talk to our patients and try to help them make the best decisions for them to take into consideration toxicity and efficacy, and really try to help them make the best informed decision that can optimize their treatment.

So we want to take what we’ve done so far. We’ve actually gotten some refreshed data from the database since the initial abstract was published, and that includes also progression-free survival data. So we’re going to put all that together, try to address some of the potential limitations, and put this into kind of the context of what we know from literature, and publish that hopefully later this year.

Closing thoughts?

I just want to thank everybody who worked with me on this. This wasn’t done just by myself alone. And we have an amazing team at Fox Chase. And specifically for this study, we have a really great statistician, Beth Handorf, and our senior author and mentor, Dr. [inaudible], as well as some other colleagues who helped us put this together, so I thank them.