Erdafitinib prolongs recurrence-free survival in high-risk NMIBC

Oral erdafitinib (Balversa) led to an improvement in recurrence-free survival (RFS) compared with chemotherapy in patients with high-risk non–muscle-invasive bladder cancer (HR NMIBC) and select fibroblast growth factor receptor (FGFR) alterations who had received prior BCG therapy, according to data from cohort 1 of the phase 2 THOR-2 trial (NCT04172675) presented at the 2023 European Society for Medical Oncology (ESMO) Annual Congress in Madrid, Spain.¹

At a median follow-up of 13.4 months, the median RFS had not yet been met for oral erdafitinib, vs a median 11.6 months for chemotherapy (HR, 0.28; 95% CI, 0.1-0.6; nominal P = .008). In other words, oral erdafitinib led to a 72% reduced risk of disease recurrence or death compared with chemotherapy.

James W.F. Catto, PhD, FRCS

"Patients with NMIBC who experience disease recurrence after BCG treatment have limited treatment options, and those eligible patients with FGFR alterations who received erdafitinib in the THOR-2 trial had far fewer recurrences against patients treated by the current standard of care. Our findings underscore the importance of detecting certain genetic biomarkers to identify patients who may benefit from treatment with a targeted therapy like erdafitinib,” presenting author James W.F. Catto, PhD, FRCS, said in a news release on the findings.² Catto is a professor in the department of oncology and metabolism at the University of Sheffield in the UK.

In total, the THOR-2 study included 73 adult patients with recurrent, BCG-treated, papillary-only HR NMIBC. Patients were randomly assigned 2:1 to receive 6 mg oral erdafitinib (n = 49) or standard of care chemotherapy (n = 24) with either gemcitabine or mitomycin C. The primary end point was RFS. Secondary end points included RFS at 6 and 12 months and safety.

At 6 months, the RFS rate for those in the erdafitinib group was 96%, compared with 73% for those in the chemotherapy group. At 12 months, RFS rate for erdafitinib was 77%, compared with 41% for chemotherapy. At the time of data cutoff, 25 total RFS events had occurred, with 11 in the erdafitinib arm and 14 in the chemotherapy arm.

The safety profile for erdafitinib was consistent with known safety profiles for oral FGFR inhibitors. Grade 3 or 4 treatment-related adverse events (AEs) were reported in 15 patients who received erdafitinib and in 1 patient who received chemotherapy. In total, 28.6% of patients in the erdafitinib arm discontinued treatment due to AEs, and no treatment-related deaths were reported. In the chemotherapy arm, no treatment-related discontinuations or deaths were reported.

Despite the positive outcomes regarding RFS, Catto noted that there is still a need to limit toxicity in these patients.

“There’s a 72% less chance of recurrence with oral erdafitinib than with standard of care. The problem is tolerability. All patients had [adverse] effects with erdafitinib, and a third of them had to stop the drug because of the toxicity,” Catto stated in an interview with Urology Times at ESMO. “In the long run, I think it's a very active product, but perhaps an orally active systemic treatment is not the right one for a localized disease. As a consequence, we're now looking at the TAR-210, which is a drug loaded stent [that] sits in the bladder and has erdafitinib with it.”

Data from a phase 1 study of TAR-210 (NCT05316155), a novel intravesical system to deliver erdafitinib, were also presented at ESMO and showed initial safety and tolerability in patients with NMIBC and FGFR alterations.³

The authors from the TAR-210 study concluded, “Results justify further study of targeted [treatment] of erdafitinib using a novel intravesical delivery system in early-stage bladder cancer.”

References

1. THOR-2 cohort 1: Results of erdafitinib (ERDA) vs intravesical chemotherapy (chemo) in patients (pts) with high-risk non-muscle-invasive bladder cancer (HR NMIBC) with select fibroblast growth factor receptor alterations (FGFRALT) who received prior bacillus calmette-guérin (BCG) treatment. Presented at the European Society of Medical Oncology (ESMO) Congress. October 20-24, 2023. Madrid, Spain. Abstract LBA102

2. Results from phase 2 THOR-2 study show improved rates of recurrence-free survival in patients with high-risk non-muscle-invasive bladder cancer with select fibroblast growth factor receptor alterations treated with BALVERSA (erdafitinib) versus chemotherapy. News release. Janssen Pharmaceutical Companies of Johnson & Johnson. October 21, 2023. Accessed October 24, 2023. https://www.prnewswire.com/news-releases/results-from-phase-2-thor-2-study-show-improved-rates-of-recurrence-free-survival-in-patients-with-high-risk-non-muscle-invasive-bladder-cancer-with-select-fibroblast-growth-factor-receptor-alterations-treated-with-balversa-erda-301963725.html

3. First safety and efficacy results of the TAR-210 erdafitinib (erda) intravesical delivery system in patients (pts) with non-muscle-invasive bladder cancer (NMIBC) with select FGFR alterations (alt). Presented at the European Society of Medical Oncology (ESMO) Congress. October 20-24, 2023. Madrid, Spain. Abstract LBA104