Targeting FGFR Mutations in Metastatic Urothelial Cancer - Episode 13

Future Outlook on the Management of Metastatic Urothelial Cancer


Drs Arlene O. Siefker-Radtke and Scott T. Tagawa consider how the urology field will likely advance with more interest in genomic profiling in metastatic urothelial cancer and novel therapies in the pipeline.

Arlene O. Siefker-Radtke, MD: Now that we’ve talked about toxicity and activity, I want to ask you, where are the unmet needs? Where do you see us moving in the future with FGF-targeted agents?

Scott T. Tagawa, MD, MS, FACP: You mentioned additional lines of therapy. The NORSE trial, as you mentioned, looked very interesting. Small numbers but looked very interesting in terms of response rates. And that’s in the first-line setting for noncisplatin candidates who had an FGFR-activating alteration. That looks very interesting, especially if the hypothesis is that PD-1 or PD-L1 immune checkpoint inhibition alone is even worse than that situation. But that’s a route going forward.

The most common disease state or stage at diagnosis of urothelial carcinoma is nonmuscle invasive. Nonmuscle invasive is also the most common with FGFR alterations as you mentioned before. Some do quite well with a good TRB [total resection of bladder] with or without intravesical therapy. But for these, they’re not all cured, and it can be a chronically recurrent disease state and then there’s that subset who have BCG-resistant disease. This disease state is so prevalent that it’s the other natural place to go with FGFR inhibition.

Arlene O. Siefker-Radtke, MD: We’re seeing a lot of development of FGFR3 inhibitors in general. We have an accelerated approval for erdafitinib in patients who’ve had prior treatment for urothelial cancer and have surgically unresectable or metastatic disease. But there are a lot of trials ongoing, combining erdafitinib and otherFGF inhibitors with immune checkpoint inhibitors to see if we can overcome mechanisms associated with resistance to immunotherapy. Then we’re studying FGF-targeted agents in earlier stages where they may play a role in biology, yet toxicity management may be key.

There’s certainly a lot of opportunities for use of FGF-targeted strategies in bladder cancer, a lot of trials that are ongoing. I encourage everyone in the community, if you have a patient with an FGF alteration, to consider sending them to your academic center nearby so we can enroll them on several of these or any of these clinical trials as we try to move the field forward. And help improve the treatment of all patients with urothelial cancer, including those withFGFR3alterations present.

I’d like to thank you all for your time. I’d like to thank my colleague Dr Tagawa for providing his insights into how we’re managing these patients with urothelial cancer, looking at biomarkers, and managing toxicities of FGFR3-targeted therapy. I’d like to thank OncLive® as well for supporting this work so that we can bring this information to the community physicians who are taking care of large numbers of patients during the challenges of this pandemic. Thank you again for your time.

Transcript edited for clarity.