Bladder Cancer - Episode 12

Case 3: Treatment for FGFR3+ Bladder Cancer

November 27, 2019


Arlene O. Siefker-Radtke, MD:I’d like to ask Gordon, is there anything else that you think we should look into for this patient before we move on to treatment?

Gordon Brown, DO:No. From a urology perspective, I think he’s been actually fairly well evaluated. He already has evidence of metastatic disease. As long as we have adequate tissue to interrogate as it relates to molecular marker evaluation, which has been done, and his local symptoms are controlled, I think we would not have much more to intervene with at this point for him.

Arlene O. Siefker-Radtke, MD:Right. So moving on to treatment. We now have someone who’s failed platinum-based chemotherapy with progressive disease, and we have a detectable mutation, but PD-L1 [programmed death-ligand 1]—low. However, immunotherapy does not require presence of PD-L1 to be tested in the second-line setting. I’m curious, Betsy, what would you recommend as the next line of treatment for this case?

Elizabeth R. Plimack, MD:This is a tough question. Obviously thisFGFRmutation is very tantalizing. We now have a targeted therapy, erdafitinib, that targets FGFR. The response rates are impressive. But at the same time immunotherapy, as we just discussed, offers a possibility of potentially adverse-effect-free, potentially durable response and survival.

So do you go with the agent that’s more likely to achieve a response based on the target being there? Or do you take a chance with immunotherapy where the target is not there, although again, not required in the second-line space, and we have seen responses in the second-line in PD-L1—negative patients, going for a better quality of life and response?

And here’s where I would really have a discussion with the patient I think and ask about their priorities. Also, informing this would be any threatening lesions or impending disease-related symptomatology that I see coming in the short term that would lead me toward erdafitinib. But I would say it’s great to have both options. Again, it’s not either/or necessarily. It’s which one to try next usually.

Arlene O. Siefker-Radtke, MD:I heard you say, if there was something threatening, I’d take that to mean rapidly progressive disease or a lot of symptoms, would that cause you to choose erdafitinib versus immunotherapy?

Elizabeth R. Plimack, MD:I think it would. I think the response rate percentage-wise is higher there. The patient does have this alteration, so we know they’re a candidate for it. And again, if it’s not tolerated, we can dose adjust or dose reduce to get it to be tolerated more long term, and we’ll always have immunotherapy as an option.

Arlene O. Siefker-Radtke, MD:And I’ll be honest, that has been my preference with the work I’ve done on erdafitinib—and for full disclosure, I was involved in that trial. But I have seen dramatic responses, even in rapidly growing liver metastases, with symptomatology improving within 1 to 2 weeks of starting therapy. So one thing that erdafitinib does have for that rapidly progressive patient, it does have that potential to improve symptoms.

Tian Zhang, MD:That’s really why we want this, the molecular testing, early, right? One thing I’ve been stressing with our pathology department, with urology is in that high-risk patient, let’s screen them early, let’s get that molecular information so that if this patient becomes metastatic or we’re dealing with a platinum-refractory patient, we have that information. And if thisFGFR3mutation or translocation is actually driving their tumor, then these patients are actually less likely to respond to immunotherapy and more likely to respond to our erdafitinib, new standard of care for these patients.

Now in the trial that you presented nicely at ASCO [American Society of Clinical Oncology 2018 annual meeting], only 5% of these patients had a previous response to immunotherapy; whereas 59% of them responded to erdafitinib in this very refractory setting. So I think that the earlier we get the molecular testing, the earlier we would have our ducks in a row to know what next to treat the patient with.

Transcript edited for clarity.