FGFR Inhibition: A Novel Therapeutic Strategy - Episode 6

FGFR Inhibitors for CCA & Bladder Cancer

June 21, 2019

Sumanta Pal, MD:Beyond infigratinib, erdafitinib, and anti-FGFR3 [fibroblast growth factor receptor 3] monoclonal antibody B-701 vofatamab, which I mentioned previously, there are a couple of early stage compounds that are in development. One of those is from Debiopharm Group, and that particular agent blocksFGFRquite potently but seems to have more activity in the subset of patients with fusions. And there, I believe, are some studies in development with this compound. I just don’t think we have the clinical data that we need to juxtapose that particular subset of patients against other datasets that we’ve seen for erdafitinib and infigratinib at this point.

Richard Kim, MD:So there are other FGFR inhibitors that are out there as well. Any other comments on TAS-120 or other FGFR inhibitors that are out there?

Rachna Shroff, MD, MS:You know I’ll say that the data that was the most robust and most mature was infigratinib, it was the first one that really looked promising. But as mentioned, pemigatinib as well, is looking very promising. In that patient population there was a larger percent of patients who are getting this in the second-line setting. That higher response rate is probably related to the fact that these patients are getting it earlier.

And TAS-120 also is, in my opinion, a pretty exciting FGFR inhibitor. It had an arm that allowed patients to have had prior FGFR inhibitor therapy. And so we did have patients that are on the infigratinib study that then went on to TAS-120. What was notable about that study is that the patients were responding as if they’d never had prior FGFR therapy, and they were also responding even when they’d seen prior infigratinib, which is the main drug that they had gotten previously

So that also suggests that there may be a role if we have multiple drugs available in terms of the FGFR class of drugs, that there may be a role in sequencing these therapies, which is a fantastic option for our patients. And so I think we need to delve a little bit deeper into understanding FGFR resistance and whether you can give subsequent FGFR therapy.

Richard Kim, MD:Thank you. In your opinion, how does this response in a single agent sort of compare to other options that we have in second-line chemotherapy. What were other targeted agents, in your opinion?

Rachna Shroff, MD, MS:I think that it is a response that is clinically meaningful. I’m sure you’ve had patients like this too who go on and, within a few months, are feeling better. The pain is better, energy is improving, and so response, duration of response and disease control rate, are clinically meaningful endpoints. Infigratinib, in particular, has a response rate in the 30% range. Those are things that are affecting the day-to-day life of patients, and their quality of life. And so I think that is what is the most provocative thing about this data is that these endpoints are not just impressive to clinicians, but they’re clinically meaningful for their patients.

Richard Kim, MD:Thank you.

Sumanta Pal, MD:When I approach patients with bladder cancer nowadays, I tend to actually get genomic profiling right from the get-go. I think this has really been a big change in my practice from a couple of years back because, frankly, a couple of years back there wasn’t too much that I can do with the results. Now with trials of agents like infigratinib, with agents like erdafitinib gaining labels and approval, I think that it’s much easier for me to access compounds that are directed at clinically relevant entities likeFGFR3, and HER2 [human epidermal growth factor receptor 2], and apply those in patients. I will say that sometimes, if you wait on gene profiling until the very end when a patient is approaching later stages of their disease, you might run into issues with tissue acquisition, and you may potentially run into time-related issues. You don’t have enough time to get that gene profiling data in a way that’s clinically meaningful to facilitate treatment. So my big plea to clinicians is to get gene profiling done very early.

Transcript edited for clarity.