At the 2023 ASCO Genitourinary Cancers Symposium, James Catto, MB, ChB, PhD, University of Sheffield, United Kingdom, presented results from cohort 2 of the phase 2 THOR-2 trial, evaluating erdafitinib among patients with bacillus Calmette-Guérin (BCG)-unresponsive, high risk, non-muscle-invasive bladder cancer with fibroblast growth factor receptor (FGFR)3/2 alterations.

Dr Catto stated, "It seems that this drug works in the selective population up to cycle 6, and so we want longer follow up to see if it's a durable response."

Transcript:

I am Jim Catto. I'm a urological surgeon from the UK, from Sheffield, and I'm a clinical academic. I'm talking about the THOR-2 study. This is a study looking at erdafitinib, which is a selective FGFR inhibitor in patients with BCG-unresponsive bladder cancer.

This is a common problem and it's very difficult to treat. Bladder cancer is one of the most common cancers and one of the most expensive, and about one-third of patients get high-grade disease for which the first-line treatment is BCG. If BCG fails, then the standard of care is bladder removal at the moment, or cystectomy. But this is probably overtreatment for a large proportion of patients. But it's difficult to work out those who need it, with life-threatening disease, from those who can be observed. So we're always keen on new treatments that could improve the treatment options.

The THOR-2 study is looking at erdafitinib, to see whether we can identify patients whose bladder cancers have got selective changes in the FGFR3 or FGFR complex, to see if we have mutations or alterations there that make those cancers particularly susceptible to needing that access and that growth pathway. And if they are, then erdafitinib itself will block that access, and reduce that cancer and make it disappear. We've had some great results in more advanced disease and therefore, we're now moving the drug into the earlier phase.

THOR-2 is looking at people with BCG-unresponsive, non-muscle-invasive disease. There are 3 cohorts, and the cohort we're talking about today is Cohort 2, which is people who have got flat carcinoma in situ, which is BCG-unresponsive.

Within THOR-2, a large number of patients were screened for suitability, and 10 patients were recruited, of whom 1 of them was inaccurate, so shouldn't have been involved. At reporting, we had 9 patients who received erdafitinib, their average age of 72. And of those patients, they received the drug for about 5.9 months in total, that was the median month.

The evaluations we've got today are the first checkpoint, which is at cycle 3, day 1, and the second checkpoint, which is at cycle 6, day 6. And I'm pleased to see that we've had some really encouraging results. At the first point of our evaluation, we had 100% complete response rate, no carcinoma in situ, no residual tumor, in 9 out of the 9 evaluable patients. The second evaluation, at cycle 6, we had a 75% response rate, 6 out of 8 patients had a complete response of those who were evaluable. The median duration response was 3 months.

Most of the treatment side effects were relatively mild, including a dry mouth, high blood phosphate, high 50% patients got a mild diarrhea. One patient had a retinal detachment, for which they had to stop the erdafitinib, and 1 patient had subretinal fluid, for which they also had to stop. There were 3 patients who had grade 3 side effects, including a dry mouth, stomatitis, nail disorders, acute kidney injury, chronic kidney injury, and some sepsis and hypertension.

Going forward, it seems that this drug works in the selective population at up to cycle 6, and so we want longer follow up to see if it's a durable response. The toxicity profile is generally favorable, certainly if you compare it with radical surgery and the other treatment options. We're now looking for longer term data, or perhaps alternate ways of delivering the drug more locally into the bladder.

Source:

Catto JWF, Tran B, Master VA, et al. Phase 2 study of the efficacy and safety of erdafitinib in patients (pts) with bacillus Calmette-Guérin (BCG)-unresponsive, high-risk non-muscle-invasive bladder cancer (HR-NMIBC) with FGFR3/2 alterations (alt) in THOR-2: Cohort 2 interim analysis. Presented at 2023 ASCO Genitourinary Cancers Symposium; February 17-19; San Francisco, CA. Abstract 503