Journal article
Antiadenovirus Antibodies Predict Response Durability to Nadofaragene Firadenovec Therapy in BCG-unresponsive Non–muscle-invasive Bladder Cancer: Secondary Analysis of a Phase 3 Clinical Trial
European urology, Vol.81(3), pp.223-228
03/2022
DOI: 10.1016/j.eururo.2021.12.009
PMCID: PMC8891058
PMID: 34933753
Abstract
High post-treatment serum antiadenovirus antibody levels were associated with durable response to nadofaragene firadenovec. This assay could provide clinical utility in predicting response durability as a companion marker for this novel agent in bacillus Calmette-Guérin–unresponsive non–muscle-invasive bladder cancer.
A recent phase 3 trial of intravesical nadofaragene firadenovec reported a promising complete response rate for patients with bacillus Calmette-Guérin–unresponsive non–muscle-invasive bladder cancer. This study examined the ability of antiadenovirus antibody levels to predict the durability of therapeutic response to nadofaragene firadenovec. A standardized and validated quantitative assay was used to prospectively assess baseline and post-treatment serum antibody levels among 91 patients from the phase 3 trial, of whom 47 (52%) were high-grade recurrence free at 12 mo (responders). While baseline titers did not predict treatment response, 3-mo titer >800 was associated with a higher likelihood of durable response (p = 0.026). Peak post-treatment titers >800 were noted in 42 (89%) responders versus 26 (59%) nonresponders (p = 0.001; assay sensitivity, 89%; negative predictive value, 78%). Moreover, 22 (47%) responders compared with eight (18%) nonresponders had a combination of peak post-treatment titers >800 and peak antibody fold change >8 (p = 0.004; assay specificity, 82%; positive predictive value, 73%). A majority of responders continued to have post-treatment antibody titers >800 after the first 6 mo of therapy. In conclusion, serum antiadenovirus antibody quantification may serve as a novel predictive marker for nadofaragene firadenovec response durability. Future studies will focus on large-scale validation and clinical utility of the assay.
This study reports on a planned secondary analysis of a phase 3 multicenter clinical trial that established the benefit of nadofaragene firadenovec, a novel intravesical gene therapeutic, for the treatment of patients with bacillus Calmette-Guérin (BCG)-unresponsive high-risk non–muscle-invasive bladder cancer. Prospective assessment of serum anti–human adenovirus type-5 antibody levels of patients in this trial indicated that a combination of post-treatment titers and fold change from baseline can predict treatment efficacy. While this merits additional validation, our findings suggest that serum antiadenovirus antibody levels can serve as an important predictive marker for the durability of therapeutic response to nadofaragene firadenovec.
Details
- Title: Subtitle
- Antiadenovirus Antibodies Predict Response Durability to Nadofaragene Firadenovec Therapy in BCG-unresponsive Non–muscle-invasive Bladder Cancer: Secondary Analysis of a Phase 3 Clinical Trial
- Creators
- Anirban P. Mitra - The University of Texas MD Anderson Cancer CenterVikram M. Narayan - The University of Texas MD Anderson Cancer CenterSharada Mokkapati - The University of Texas MD Anderson Cancer CenterTanner Miest - The University of Texas MD Anderson Cancer CenterStephen A. Boorjian - Mayo Clinic in ArizonaMehrdad Alemozaffar - Kaiser PermanenteBadrinath R. Konety - Rush Medical CollegeNeal D. Shore - Carolina Urologic Research CenterLeonard G. Gomella - Thomas Jefferson UniversityAshish M. Kamat - The University of Texas MD Anderson Cancer CenterTrinity J. Bivalacqua - Johns Hopkins UniversityJeffrey S. Montgomery - University of MichiganSeth P. Lerner - Baylor College of MedicineJ. Erik Busby - Prisma HealthMichael Poch - Moffitt Cancer CenterPaul L. Crispen - University of FloridaGary D. Steinberg - NYU Langone HealthAnne K. Schuckman - University of Southern CaliforniaTracy M. Downs - University of Wisconsin–MadisonRobert S. Svatek - The University of Texas Health Science Center at San AntonioJoseph Mashni - The University of Texas MD Anderson Cancer CenterBrian R. Lane - Michigan State UniversityThomas J. Guzzo - University of PennsylvaniaGennady Bratslavsky - SUNY Upstate Medical UniversityLawrence I. Karsh - The Urology Center of ColoradoMichael E. Woods - Loyola University ChicagoGordon A. Brown - New Jersey UrologyDaniel Canter - Georgia UrologyAdam Luchey - West Virginia UniversityYair Lotan - The University of Texas Southwestern Medical CenterTracey Krupski - University of VirginiaBrant A. Inman - Duke UniversityMichael B. Williams - Urology of VirginiaMichael S. Cookson - University of Oklahoma Health Sciences CenterKirk A. Keegan - Vanderbilt University Medical CenterGerald L. Andriole - Washington University in St. LouisAlexander I. Sankin - Albert Einstein College of MedicineAlan Boyd - Boyds (United Kingdom)Michael A. O'Donnell - University of IowaRichard Philipson - Trizell Ltd, Chinnor, UK.Seppo Ylä-Herttuala - University of Eastern FinlandDavid Sawutz - Etelä-Karjalan sosiaali ja terveyspiiriNigel R. Parker - University of Eastern FinlandDavid J. McConkey - Johns Hopkins UniversityColin P.N. Dinney - The University of Texas MD Anderson Cancer Center
- Resource Type
- Journal article
- Publication Details
- European urology, Vol.81(3), pp.223-228
- DOI
- 10.1016/j.eururo.2021.12.009
- PMID
- 34933753
- PMCID
- PMC8891058
- NLM abbreviation
- Eur Urol
- ISSN
- 0302-2838
- eISSN
- 1873-7560
- Publisher
- Elsevier B.V
- Language
- English
- Date published
- 03/2022
- Academic Unit
- Urology
- Record Identifier
- 9984320067502771
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