Erdafitinib helps prevent recurrence in BCG-treated high-risk NMIBC

Recurrence-free survival (RFS) is significantly longer with erdafitinib treatment than with intravesical chemotherapy in patients with papillary-only, high-risk nonmuscle-invasive bladder cancer (NMIBC) who had disease recurrence after bacillus Calmette–Guérin (BCG) therapy and were ineligible for radical cystectomy, according to a study.

“[O]ur findings demonstrate that oral erdafitinib reduced the rate of recurrence or death over intravesical chemotherapy in patients with high-risk resected papillary Ta/T1 NMIBC harbouring fibroblast growth factor receptor (FGFR) mutations or fusions with recurrence after BCG treatment and who refused or were ineligible for radical cystectomy,” the researchers said.

The study enrolled patients aged ≥18 years with recurrent, BCG-treated, papillary-only high-risk NMIBC (high-grade Ta/T1) and select FGFR alterations refusing or ineligible for radical cystectomy. Participants were randomized to daily oral erdafitinib 6 mg or researcher’s choice of intravesical chemotherapy (mitomycin C or gemcitabine). RFS was the primary endpoint, while safety was secondary.

Enrolment of participants was discontinued because of slow accrual. Prior to discontinuation, 73 patients were randomly assigned 2:1 to received erdafitinib (n=49) or chemotherapy (n=24). They were followed-up for 13.4 months. [Ann Oncol 2024;35:98-106]

The erdafitinib arm did not reach the median RFS (95 percent confidence interval [CI], 16.9 months‒not estimable), while the chemotherapy group achieved a median RFS of 11.6 months (95 percent CI, 6.4‒20.1 months). The estimated hazard ratio was 0.28 (95 percent CI, 0.1‒0.6; p=0.0008).

No new safety signals were reported for both erdafitinib and chemotherapy. Tolerability with erdafitinib treatment was manageable. However, discontinuation due to treatment-related adverse events occurred more frequently with erdafitinib than with intravesical chemotherapy (29 percent vs 0 percent).

Treatment-related deaths were not reported in either group, but three deaths unrelated to treatment occurred in the erdafitinib group following discontinuation.

“The rate of erdafitinib discontinuation in this NMIBC population was higher than in previously reported clinical studies of erdafitinib in patients with locally advanced or metastatic urothelial cancer (29 percent vs 16 percent),” the researchers said. [Lancet Oncol 2022;23:248-258]

This finding underscored the “lower tolerance to adverse events in the localized disease setting of NMIBC compared with metastatic urothelial cancer and the challenges associated with managing NMIBC with systemic therapies,” according to the researchers. [Front Oncol 2023;131170124]

Antitumour activity

In patients with metastasis, erdafitinib 6 mg demonstrated antitumour activity (n=78; objective response rate, 35 percent). The median treatment duration for 8-mg erdafitinib with uptitration was 5.3 months. [N Engl J Med 2019;381:338-348]

“Given the observed antitumour activity of erdafitinib and the tolerability challenges noted in this study, local delivery that reduces systemic toxicities represents an opportunity to change the treatment landscape for patients with NMIBC and FGFR alterations,” the researchers said.

“Accordingly, a first-in-human study evaluating the novel intravesical drug delivery system, TAR-210, designed to provide sustained, local release of erdafitinib within the bladder while limiting systemic exposure, is ongoing,” they added.