Analysis of real-world re-induction outcomes with nadofaragene firadenovec in patients with Bacillus Calmette-Guérin (BCG)-unresponsive non-muscle-invasive bladder cancer.

Nadofaragene firadenovec is an intravesical gene therapy approved for use in patients with Bacillus Calmette-Guérin (BCG)-unresponsive non-muscle-invasive bladder cancer who have carcinoma in situ (CIS) with/without papillary disease (Ta or T1). It is administered every 3 months for as long as the patient maintains a complete response (CR). In the phase 2 and 3 clinical trial program, patients without CR at 3 months were not re-treated with nadofaragene firadenovec; however, many immune therapies do benefit from re-induction of this kind. We report findings from an observational cohort study of patients who underwent re-induction with nadofaragene firadenovec in a real-world setting. Electronic health records from US Specialty Networks private urology practices were used to identify patients with urothelial CIS with/without papillary disease (Ta or T1) who (I) underwent induction with intravesical nadofaragene firadenovec therapy; (II) failed to achieve a CR 3 months after the first dose but subsequently received ≥1 re-induction dose; and (III) had ≥1 follow-up cystoscopy examination. In total, 13 male patients [CIS alone (n=8), CIS + Ta (n=2), CIS + T1 (n=3)], aged (mean) 77.5 years, satisfied the study eligibility criteria. Patients had received a mean of 11 prior BCG doses; other prior therapy included gemcitabine (n=4) and pembrolizumab (n=5). Median follow-up was 379 (range, 135-519) days. After the first re-induction dose (Dose 2) of nadofaragene firadenovec, four patients (30.8%) achieved a CR, including two patients with CIS + T1. Of the patients with a CR, three received subsequent maintenance doses: one patient maintained a CR after Doses 3 and 4; one patient showed disease persistence/recurrence after Dose 4, and one patient progressed to T2a disease 15 months after re-induction. Nine patients experienced treatment failure after first re-induction with nadofaragene firadenovec; two received a second re-induction dose without response. In this real-world cohort, approximately 30% of patients achieved a CR after re-induction with nadofaragene firadenovec, supporting the proof of concept of this approach.