%0 Journal Article
%T Efficacy of Intravesical Nadofaragene Firadenovec for Patients With Bacillus Calmette-Guérin-Unresponsive Nonmuscle-Invasive Bladder Cancer: 5-Year Follow-Up From a Phase 3 Trial.
%A Narayan VM
%A Boorjian SA
%A Alemozaffar M
%A Konety BR
%A Shore ND
%A Gomella LG
%A Kamat AM
%A Bivalacqua TJ
%A Montgomery JS
%A Lerner SP
%A Busby JE
%A Poch M
%A Crispen PL
%A Steinberg GD
%A Schuckman AK
%A Downs TM
%A Mashni J
%A Lane BR
%A Guzzo TJ
%A Bratslavsky G
%A Karsh LI
%A Woods ME
%A Brown G
%A Canter D
%A Luchey A
%A Lotan Y
%A Inman BA
%A Williams MB
%A Cookson MS
%A Chang SS
%A Sankin AI
%A O'Donnell MA
%A Sawutz D
%A Philipson R
%A Parker NR
%A Yla-Herttuala S
%A Rehm D
%A Jakobsen JS
%A Juul K
%A Dinney CPN
%J J Urol
%V 212
%N 1
%D 2024 Jul 5
%M 38704840
%F 7.6
%R 10.1097/JU.0000000000004020
%X <B>UNASSIGNED: </B>Nadofaragene firadenovec-vncg is a nonreplicating adenoviral vector-based gene therapy for bacillus Calmette-Guérin (BCG)-unresponsive carcinoma in situ (CIS) with/without high-grade Ta/T1. We report outcomes following 5 years of planned follow-up.<BR><B>UNASSIGNED: </B>This open-label phase 3 trial (NCT02773849) enrolled patients with BCG-unresponsive nonmuscle-invasive bladder cancer in 2 cohorts: CIS ± Ta/T1 (CIS; n = 107) and Ta/T1 without CIS (Ta/T1 cohort; n = 50). Patients received 75 mL (3 × 1011 vp/mL) nadofaragene firadenovec intravesically once every 3 months with cystoscopy and cytology assessments, with continued treatment offered to those remaining high grade recurrence-free (HGRF).<BR><B>UNASSIGNED: </B>One hundred fifty-seven patients were enrolled from 33 US sites (n = 151 included in efficacy analyses). Median follow-up was 50.8 months (interquartile range 39.1-60.0), with 27% receiving ≥ 5 instillations and 7.6% receiving treatment for ≥ 57 months. Of patients with CIS 5.8% (95% CI 2.2-12.2) were HGRF at month 57, and 15% (95% CI 6.1-27.8) of patients with high-grade Ta/T1 were HGRF at month 57. Kaplan-Meier-estimated HGRF survival at 57 months was 13% (95% CI 6.9-21.5) and 33% (95% CI 19.5-46.6) in the CIS and Ta/T1 cohorts, respectively. Cystectomy-free survival at month 60 was 49% (95% CI 40.0-57.1): 43% (95% CI 32.2-53.7) in the CIS cohort and 59% (95% CI 43.1-71.4) in the Ta/T1 cohort. Overall survival at 60 months was 80% (71.0, 86.0): 76% (64.6-84.5) and 86% (70.9-93.5) in the CIS and Ta/T1 cohorts, respectively. Only 5 patients (4 with CIS and 1 with Ta/T1) experienced clinical progression to muscle-invasive disease.<BR><B>UNASSIGNED: </B>At 60 months, nadofaragene firadenovec-vncg allowed bladder preservation in nearly half of the patients and proved to be a safe option for BCG-unresponsive nonmuscle-invasive bladder cancer.