TY - JOUR
T1 - Antiadenovirus Antibodies Predict Response Durability to Nadofaragene Firadenovec Therapy in BCG-unresponsive Non–muscle-invasive Bladder Cancer
T2 - Secondary Analysis of a Phase 3 Clinical Trial
AU - Mitra, Anirban P.
AU - Narayan, Vikram M.
AU - Mokkapati, Sharada
AU - Miest, Tanner
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, J. Erik
AU - Poch, Michael
AU - Crispen, Paul L.
AU - Steinberg, Gary D.
AU - Schuckman, Anne K.
AU - Downs, Tracy M.
AU - Svatek, Robert S.
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 A.
AU - Canter, Daniel
AU - Luchey, Adam
AU - Lotan, Yair
AU - Krupski, Tracey
AU - Inman, Brant A.
AU - Williams, Michael B.
AU - Cookson, Michael S.
AU - Keegan, Kirk A.
AU - Andriole, Gerald L.
AU - Sankin, Alexander I.
AU - Boyd, Alan
AU - O'Donnell, Michael A.
AU - Philipson, Richard
AU - Ylä-Herttuala, Seppo
AU - Sawutz, David
AU - Parker, Nigel R.
AU - McConkey, David J.
AU - Dinney, Colin P.N.
N1 - Publisher Copyright:
© 2021 European Association of Urology
PY - 2022/3
Y1 - 2022/3
N2 - 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. Patient summary: 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.
AB - 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. Patient summary: 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.
KW - Antiadenovirus antibody
KW - Bladder cancer
KW - Companion biomarker
KW - Gene therapy
KW - Treatment efficacy
UR - http://www.scopus.com/inward/record.url?scp=85121351767&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85121351767&partnerID=8YFLogxK
U2 - 10.1016/j.eururo.2021.12.009
DO - 10.1016/j.eururo.2021.12.009
M3 - Article
C2 - 34933753
AN - SCOPUS:85121351767
SN - 0302-2838
VL - 81
SP - 223
EP - 228
JO - European Urology
JF - European Urology
IS - 3
ER -