Erdafitinib demonstrates efficacy in intermediate-risk non–muscle-invasive bladder cancer with FGFR alterations

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Published: 18 Feb 2023
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Prof Siamak Daneshmand - University of Southern California, Los Angeles, USA

Prof Siamak Daneshmand speaks to ecancer at ASCO GU 2023 about the cohort 3 interim analysis of THOR-2, a phase 2 study of the efficacy and safety of erdafitinib in patients with intermediate-risk non–muscle-invasive bladder cancer with FGFR3/2 alterations.

He explains the primary exploratory end point for the study was the disappearance of the marker lesion without any new lesions; if there is a remnant of the marker lesion, no viable tumour should be seen on histopathological examination. The key secondary end point was safety for intermediate-risk non–muscle-invasive bladder cancer patients.

Prof Daneshmand concludes that data from cohort 3 of THOR-2 demonstrated an efficacy in adult patients with intermediate-risk non–muscle-invasive bladder cancer with FGFR alterations treated with erdafitinib. Safety data was also consistent with the known safety profile of erdafitinib.

The THOR-2 study cohort 3, which is being presented here alongside with another cohort, 2, was the use of erdafitinib in intermediate risk bladder cancer. This was an additional cohort opened up for 20 patients with intermediate risk bladder cancer, which includes recurrent low-grade tumours and small high-grade tumours. So we know that these FGFR3 mutations are far more common in patients with low-grade tumours so it’s the perfect cohort to examine the efficacy and safety of erdafitinib in this group.

Again, this is part of a cohort of this other trial, the CORE-001 and -002, that is being run for the BCG unresponsive disease. So we enrolled approximately 20 patients worldwide and we are presenting the first ten patients who were evaluable here.

The methodology was basically any patient who came in who was deemed to have recurrent low-grade tumour or, again, a high-grade tumour that was less than 3cm, that is in that AUA intermediate risk category, was eligible for the study. Their tumour tissue was sent for FGFR testing and if they are positive they can be enrolled in the trial. This is a unique design for this trial – we would remove all the tumours except leave one marker lesion behind to see the efficacy of the drug. So you had to leave a small tumour behind. Generally deemed to be very safe because these are low-grade tumours, the progression rates are very low. Once the patients were enrolled then we would start them on oral erdafitinib at the 6mg dose and do a safety check cystoscopy at six weeks and again at the routine intervals of three months, six months and nine months. The patients were given oral erdafitinib daily for three out of four weeks.

This is really exciting because this is the first time we’re using an oral medication to eradicate tumours in the bladder. Everyone is concentrating on intravesical therapies and we really don’t have a lot of therapies for these patients; with these recurrent intermediate-risk patients there are a few trials coming along but in general we’ve either been doing nothing, especially in the BCG shortage era, we do have chemotherapy available. But this is an oral medication that avoids those toxicities and the catheterisations and things like that.

The results for the ten patients that are being presented here, nine of them were evaluable and six of the eight who had follow-up had a complete response. So it’s really fascinating, when I say complete response either tumours that we had left behind, took pictures of, on our cystoscopy they had completely disappeared. So really amazing and it’s very, very quick. Many of them at six weeks we had seen already the disappearance of the tumour. Again, six of the eight had complete disappearance and fairly durable response. Now, their follow-up is short right now and we do have 20 patients overall so I know we have some more encouraging results to present later.

This is very exciting data. I can imagine that in the future if patients get these recurrent tumours, instead of taking them to the operating room, doing another resection and finding out the pathology, putting them… These are difficult surgeries for patients sometimes to get through, there are a lot of irritative voiding symptoms and things like that. So if we scope them in the clinic and they have recurrent tumours perhaps we can treat them with a short course, a short duration, of oral medication and really have the tumours be eradicated if they harbour the FGFR3 mutation. 

The nice thing is, once you have the mutation the subsequent tumours generally have the same biology so we don’t have to keep checking for the tumours once we know the biology, perhaps. What I am envisioning is we treat the patients, have a drug-free period and if they have a recurrence rechallenge them with the medicine. So it’s a really shifting paradigm in how we generally manage bladder tumours that are recurrent who end up going to the operating room for these repeated procedures.

The message here is that there are novel mechanisms outside of what we’ve generally been treating patients with; there are novel delivery mechanisms. Actually, the next step is putting the oral erdafitinib as a systemic drug, putting it directly in the bladder, and that is happening with a new device called a TAR-210 where a capsule containing the device is placed in the bladder that elutes this drug over a period of time, about three weeks. Very preliminary results from that trial are being presented as a trial in progress here. Very, very encouraging to decrease the systemic side effects, so we’re beginning to think outside the box in terms of how we’re treating these patients, what we’re treating them with and the mechanism, the delivery mechanisms, of these drugs. 

So the broader picture is in the future we’re going to have an armamentarium of treatment options available for patients which is really a great thing for these patients who have had very limited treatment options in the past