Document Type
Article
Publication Date
5-5-2024
Abstract
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.
Recommended Citation
Narayan, Vikram M.; Boorjian, Stephen A.; Alemozaffar, Mehrdad; Konety, Badrinath R.; Shore, Neal D.; Gomella, Leonard G.; Kamat, Ashish M.; Bivalacqua, Trinity J.; Montgomery, Jeffrey S.; Lerner, Seth P.; Busby, Joseph E.; Poch, Michael; Crispen, Paul L.; Steinberg, Gary D.; Schuckman, Anne K.; Downs, Tracy M.; Mashni, Joseph; Lane, Brian R.; Guzzo, Thomas J.; Bratslavsky, Gennady; Karsh, Lawrence I.; Woods, Michael E.; Brown, Gordon; Canter, Daniel; Luchey, Adam; Lotan, Yair; Inman, Brant A.; Williams, Michael B.; Cookson, Michael S.; Chang, Sam S.; Sankin, Alexander I.; O'Donnell, Michael A.; Sawutz, David; Philipson, Richard; Parker, Nigel R.; Yla-Herttuala, Seppo; Rehm, Dorte; Jakobsen, Jørn S.; Juul, Kristian; and Dinney, Colin P.N., "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" (2024). Department of Urology Faculty Papers. Paper 83.
https://jdc.jefferson.edu/urologyfp/83
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.
Supplementary Table
PubMed ID
38704840
Language
English
Comments
This article is the author's final published version in the Journal of Urology, Volume 212, Issue 1, July 2024, Pg. 74 - 86.
The published version is available at https://doi.org/10.1097/JU.0000000000004020. Copyright © 2024 The Author(s). Published on behalf of the American Urological Association, Education and Research, Inc.