TY - JOUR
T1 - Efficacy of Intravesical Nadofaragene Firadenovec for Patients with Bacillus Calmette-Guérin-Unresponsive Nonmuscle-Invasive Bladder Cancer
T2 - 5-Year Follow-Up from a Phase 3 Trial
AU - Narayan, Vikram M.
AU - Boorjian, Stephen A.
AU - Alemozaffar, Mehrdad
AU - Konety, Badrinath R.
AU - Shore, Neal D.
AU - Gomella, Leonard G.
AU - Kamat, Ashish M.
AU - Bivalacqua, Trinity J.
AU - Montgomery, Jeffrey S.
AU - Lerner, Seth P.
AU - Busby, Joseph E.
AU - Poch, Michael
AU - Crispen, Paul L.
AU - Steinberg, Gary D.
AU - Schuckman, Anne K.
AU - Downs, Tracy M.
AU - Mashni, Joseph
AU - Lane, Brian R.
AU - Guzzo, Thomas J.
AU - Bratslavsky, Gennady
AU - Karsh, Lawrence I.
AU - Woods, Michael E.
AU - Brown, Gordon
AU - Canter, Daniel
AU - Luchey, Adam
AU - Lotan, Yair
AU - Inman, Brant A.
AU - Williams, Michael B.
AU - Cookson, Michael S.
AU - Chang, Sam S.
AU - Sankin, Alexander I.
AU - O'Donnell, Michael A.
AU - Sawutz, David
AU - Philipson, Richard
AU - Parker, Nigel R.
AU - Yla-Herttuala, Seppo
AU - Rehm, Dorte
AU - Jakobsen, Jørn S.
AU - Juul, Kristian
AU - Dinney, Colin P.N.
N1 - Publisher Copyright: © 2024 The Author(s). Published on behalf of the American Urological Association, Education and Research, Inc.
PY - 2024/7/1
Y1 - 2024/7/1
N2 - Purpose: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.Materials and Methods: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).Results: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.Conclusions: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.
AB - Purpose: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.Materials and Methods: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).Results: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.Conclusions: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.
KW - BCG-unresponsive bladder cancer
KW - bladder cancer
KW - gene therapy
KW - intravesical instillation
KW - nonmuscle invasive bladder cancer
UR - https://www.scopus.com/pages/publications/85195708425
U2 - 10.1097/JU.0000000000004020
DO - 10.1097/JU.0000000000004020
M3 - Article
C2 - 38704840
SN - 0022-5347
VL - 212
SP - 74
EP - 86
JO - Journal of Urology
JF - Journal of Urology
IS - 1
ER -