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

Open AccessJournal of UrologyAdult Urology5 May 2024Efficacy of Intravesical Nadofaragene Firadenovec for Patients with BCG-Unresponsive Non–muscle Invasive Bladder Cancer: 5 Year Follow-Up from a Phase 3 Trial Vikram M. Narayan, Stephen A. Boorjian, Mehrdad Alemozaffar, Badrinath R. Konety, Neal D. Shore, Leonard G. Gomella, Ashish M. Kamat, Trinity J. Bivalacqua, Jeffrey S. Montgomery, Seth P. Lerner, Joseph E. Busby, Michael Poch, Paul L. Crispen, Gary D. Steinberg, Anne K. Schuckman, Tracy M. Downs, Joseph Mashni, Brian R. Lane, Gennady Bratslavsky, Lawrence I. Karsh, Michael E. Woods, Gordon Brown, Daniel Canter, Adam Luchey, Yair Lotan, Brant A. Inman, Michael B. Williams, Michael S. Cookson, Sam S. Chang, Alexander I. Sankin, Michael A. O'Donnell, David Sawutz, Richard Philipson, Nigel R. Parker, Seppo Yla-Herttuala, Dorte Rehm, Jørn S. Jakobsen, Kristian Juul, and Colin P. N. Dinney Vikram M. NarayanVikram M. Narayan https://orcid.org/0000-0003-3731-4209 , Stephen A. BoorjianStephen A. Boorjian , Mehrdad AlemozaffarMehrdad Alemozaffar , Badrinath R. KonetyBadrinath R. Konety , Neal D. ShoreNeal D. Shore , Leonard G. GomellaLeonard G. Gomella , Ashish M. KamatAshish M. Kamat , Trinity J. BivalacquaTrinity J. Bivalacqua , Jeffrey S. MontgomeryJeffrey S. Montgomery , Seth P. LernerSeth P. Lerner , Joseph E. BusbyJoseph E. Busby , Michael PochMichael Poch , Paul L. CrispenPaul L. Crispen , Gary D. SteinbergGary D. Steinberg , Anne K. SchuckmanAnne K. Schuckman , Tracy M. DownsTracy M. Downs , Joseph MashniJoseph Mashni , Brian R. LaneBrian R. Lane , Gennady BratslavskyGennady Bratslavsky , Lawrence I. KarshLawrence I. Karsh , Michael E. WoodsMichael E. Woods , Gordon BrownGordon Brown , Daniel CanterDaniel Canter , Adam LucheyAdam Luchey , Yair LotanYair Lotan , Brant A. InmanBrant A. Inman , Michael B. WilliamsMichael B. Williams , Michael S. CooksonMichael S. Cookson , Sam S. ChangSam S. Chang , Alexander I. SankinAlexander I. Sankin , Michael A. O'DonnellMichael A. O'Donnell , David SawutzDavid Sawutz , Richard PhilipsonRichard Philipson , Nigel R. ParkerNigel R. Parker , Seppo Yla-HerttualaSeppo Yla-Herttuala , Dorte RehmDorte Rehm , Jørn S. JakobsenJørn S. Jakobsen , Kristian JuulKristian Juul , and Colin P. N. DinneyColin P. N. Dinney Corresponding Author: Colin P.N. Dinney, Department of Urology Division of Surgery, University of Texas, MD Anderson Cancer Center, Houston, TX ( ([email protected]) ). View All Author Informationhttps://doi.org/10.1097/JU.0000000000004020AboutPDF ToolsAdd to favoritesDownload CitationsTrack Citations ShareFacebookLinked InTwitterEmail Abstract Background: Nadofaragene firadenovec-vncg is a non-replicating adenoviral vector–based gene therapy for BCG-unresponsive carcinoma in situ (CIS) with/without HG Ta/T1). We report outcomes following 5 years of planned follow-up. Methods: This open-label phase 3 trial (NCT02773849) enrolled patients with BCG-unresponsive NMIBC 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) of 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 (IQR 39.1-60.0), with 27% receiving ≥ 5 instillations and 7.6% receiving treatment for ≥ 57 months. 5.8% (95% CI 2.2-12.2) of patients with CIS and 15% (95% CI 6.1-27.8) of patients with HG Ta/T1 were HGRF at month 57. Kaplan-Meier (KM)–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 NMIBC. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.© 2024 The Author(s). Published on behalf of the American Urological Association, Education and Research, Inc.FiguresReferencesRelatedDetails Supplementary Materials Advertisement Copyright & Permissions© 2024 The Author(s). Published on behalf of the American Urological Association, Education and Research, Inc.Keywordsbladder cancernon-muscle invasive bladder cancerintravesical instillationgene therapyBCG-unresponsive bladder cancerMetrics Author Information Vikram M. Narayan More articles by this author Stephen A. Boorjian More articles by this author Mehrdad Alemozaffar More articles by this author Badrinath R. Konety More articles by this author Neal D. Shore More articles by this author Leonard G. Gomella More articles by this author Ashish M. Kamat More articles by this author Trinity J. Bivalacqua More articles by this author Jeffrey S. Montgomery More articles by this author Seth P. Lerner More articles by this author Joseph E. Busby More articles by this author Michael Poch More articles by this author Paul L. Crispen More articles by this author Gary D. Steinberg More articles by this author Anne K. Schuckman More articles by this author Tracy M. Downs More articles by this author Joseph Mashni More articles by this author Brian R. Lane More articles by this author Gennady Bratslavsky More articles by this author Lawrence I. Karsh More articles by this author Michael E. Woods More articles by this author Gordon Brown More articles by this author Daniel Canter More articles by this author Adam Luchey More articles by this author Yair Lotan More articles by this author Brant A. Inman More articles by this author Michael B. Williams More articles by this author Michael S. Cookson More articles by this author Sam S. Chang More articles by this author Alexander I. Sankin More articles by this author Michael A. O'Donnell More articles by this author David Sawutz More articles by this author Richard Philipson More articles by this author Nigel R. Parker More articles by this author Seppo Yla-Herttuala More articles by this author Dorte Rehm More articles by this author Jørn S. Jakobsen More articles by this author Kristian Juul More articles by this author Colin P. N. Dinney Corresponding Author: Colin P.N. Dinney, Department of Urology Division of Surgery, University of Texas, MD Anderson Cancer Center, Houston, TX ( ([email protected]) ). More articles by this author Expand All Advertisement PDF downloadLoading ...