THOR-2 Cohort 1: Recurrence-Free Survival in FGFR-Altered NMIBC After Erdafitinib, Prior BCG

A late-breaking abstract at the European Society for Medical Oncology Congress 2023 shed light on the effects of erdafitinib versus intravesical chemotherapy in patients with high-risk non-muscle invasive bladder cancer (HR NMIBC) with select fibroblast growth factor receptor (FGFR) alterations who experienced disease recurrence after bacillus Calmette Guérin (BCG) treatment.

Current treatment options for patients with HR NMIBC who have recurrence after BCG treatment are limited, especially for those who are ineligible for or refuse radical cystectomy. In the phase 3 THOR study, erdafitinib—an oral selective pan-FGFR tyrosine kinase inhibitor—demonstrated an overall survival benefit compared with chemotherapy in patients with locally advanced or metastatic urothelial carcinoma with FGFR alterations.

James W. Catto, MB, ChB, PhD, FRCS, of the University of Sheffield, and colleagues reported the first randomized data in patients with recurrent BCG-treated HR NMIBC with FGFR alterations from cohort 1 of the THOR-2 study. A total of 73 adult patients with papillary-only HR NMIBC (high-grade Ta/T1) who were ineligible or refused radical cystectomy were randomized (2:1) to either erdafitinib (6 mg orally; n=49) or investigator’s choice of intravesical chemotherapy (mitomycin C or gemcitabine; n=24).

The primary end point was recurrence-free survival (RFS). Secondary end points included RFS rate at 6 and 12 months and safety.

After a median follow-up of 13.4 months for both groups, median RFS was not reached versus 11.6 months for the erdafitinib and chemotherapy groups, respectively (estimated hazard ratio, 0.28). Six- and 12-month RFS rates were 96% and 77% for erdafitinib, respectively, versus 73% and 41% for chemotherapy, respectively.

Dr. Catto and colleagues noted that grade 3/4 treatment-related adverse events (TRAEs) occurred in 31% and 4% of patients in the erdafitinib and chemotherapy groups, respectively. Notably, central serous retinopathy occurred in 39% of patients receiving erdafitinib and resolved in 58% of these patients.

Though study enrollment was discontinued because of slow patient accrual, Dr. Catto and colleagues concluded that erdafitinib prolonged RFS compared with chemotherapy in patients with papillary-only HR NMIBC with FGFR alterations who had recurrence after BCG treatment, adding that erdafitinib toxicity was “generally consistent” with the known safety profile of other oral FGFR inhibitors.