{Reference Type}: Journal Article
{Title}: 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.
{Author}: Narayan VM;Boorjian SA;Alemozaffar M;Konety BR;Shore ND;Gomella LG;Kamat AM;Bivalacqua TJ;Montgomery JS;Lerner SP;Busby JE;Poch M;Crispen PL;Steinberg GD;Schuckman AK;Downs TM;Mashni J;Lane BR;Guzzo TJ;Bratslavsky G;Karsh LI;Woods ME;Brown G;Canter D;Luchey A;Lotan Y;Inman BA;Williams MB;Cookson MS;Chang SS;Sankin AI;O'Donnell MA;Sawutz D;Philipson R;Parker NR;Yla-Herttuala S;Rehm D;Jakobsen JS;Juul K;Dinney CPN;
{Journal}: J Urol
{Volume}: 212
{Issue}: 1
{Year}: 2024 Jul 5
{Factor}: 7.6
{DOI}: 10.1097/JU.0000000000004020
{Abstract}: <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.