Evidence map›Paper›PMID 34933753›Full record

ArticleEuropean urology2022

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.

Anirban P Mitra, Vikram M Narayan, Sharada Mokkapati, Tanner Miest, Stephen A Boorjian, Mehrdad Alemozaffar, Badrinath R Konety, Neal D Shore, Leonard G Gomella, Ashish M Kamat and 35 more

Open access · greenAbstract readMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Article in European urology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
3.6field-weighted citation impact, top 6% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

13 citing papers in PubMed, 21 citations in OpenAlex.

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  7. The danger theory of immunity revisited.Nature reviews. Immunology · 2024
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

45 authors at 20 institutions in 3 countries.

Anirban P MitraDepartment of Urology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Vikram M NarayanDepartment of Urology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Sharada MokkapatiDepartment of Urology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Tanner MiestDepartment of Urology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Stephen A BoorjianDepartment of Urology, Mayo Clinic, Rochester, MN, USA.
Mehrdad AlemozaffarDepartment of Urology, Kaiser Permanente Los Angeles, Los Angeles, CA, USA.
Badrinath R KonetyDepartment of Urology, Rush Medical College, Chicago, IL, USA.
Neal D ShoreCarolina Urologic Research Center, Myrtle Beach, SC, USA.
Leonard G GomellaDepartment of Urology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, USA.
Ashish M KamatDepartment of Urology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Trinity J BivalacquaDepartment of Urology, The James Buchanan Brady Urological Institute, Johns Hopkins University, Baltimore, MD, USA.
Jeffrey S MontgomeryDepartment of Urology, University of Michigan, Ann Arbor, MI, USA.
Seth P LernerScott Department of Urology, Baylor College of Medicine, Houston, TX, USA.
J Erik BusbyDepartment of Surgery, Prisma Health, University of South Carolina School of Medicine at Greenville, Greenville, SC, USA.
Michael PochDepartment of Genitourinary Oncology, H Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
Paul L CrispenDepartment of Urology, University of Florida, Gainesville, FL, USA.
Gary D SteinbergDepartment of Urology, New York University Langone Health, New York, NY, USA.
Anne K SchuckmanInstitute of Urology, University of Southern California, Los Angeles, CA, USA.
Tracy M DownsDepartment of Urology, University of Wisconsin, Madison, WI, USA.
Robert S SvatekDepartment of Urology, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.
Joseph MashniDepartment of Surgical Oncology, Banner MD Anderson Cancer Center, Gilbert, AZ, USA.
Brian R LaneDivision of Urology, Spectrum Health, Michigan State University College of Human Medicine, Grand Rapids, MI, USA.
Thomas J GuzzoDivision of Urology, University of Pennsylvania, Philadelphia, PA, USA.
Gennady BratslavskyDepartment of Urology, SUNY Upstate Medical University, Syracuse, NY, USA.
Lawrence I KarshThe Urology Center of Colorado, Denver, CO, USA.
Michael E WoodsDepartment of Urology, Loyola University, Maywood, IL, USA.
Gordon A BrownNew Jersey Urology, Bloomfield, NJ, USA.
Daniel CanterGeorgia Urology, Atlanta, GA, USA.
Adam LucheyDepartment of Urology, West Virginia University Cancer Institute, Morgantown, WV, USA.
Yair LotanDepartment of Urology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Tracey KrupskiDepartment of Urology, University of Virginia, Charlottesville, VA, USA.
Brant A InmanDivision of Urology, Department of Surgery, Duke University, Durham, NC, USA.
Michael B WilliamsUrology of Virginia, Virginia Beach, VA, USA.
Michael S CooksonDepartment of Urology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
Kirk A KeeganDepartment of Urology, Vanderbilt University Medical Center, Nashville, TN, USA.
Gerald L AndrioleDivision of Urologic Surgery, Department of Surgery, Washington University School of Medicine in St Louis, St Louis, MO, USA.
Alexander I SankinDepartment of Urology, Montefiore Medical Center and Albert Einstein College of Medicine, Bronx, NY, USA.
Alan BoydBoyd Consultants Ltd, Crewe, UK.
Michael A O'DonnellDepartment of Urology, University of Iowa, Iowa City, IA, USA.
Richard PhilipsonTrizell Ltd, Chinnor, UK.
Seppo Ylä-HerttualaAI Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland.
David SawutzFKD Therapies Oy, Kuopio, Finland.
Nigel R ParkerAI Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland.
David J McConkeyDepartment of Urology, Greenberg Bladder Cancer Institute, Johns Hopkins University, Baltimore, MD, USA.
Colin P N DinneyDepartment of Urology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. Electronic address: cdinney@mdanderson.org.
The University of Texas MD Anderson Cancer Center · USJohns Hopkins University · USUniversity of Eastern Finland · FIAlbert Einstein College of Medicine · USBaylor College of Medicine · USBoyds (United Kingdom) · GBCarolina Urologic Research Center · USDuke University · USGeorgia Urology · USKaiser Permanente · USMayo Clinic in Arizona · USMichigan State University · USMoffitt Cancer Center · USNew Jersey Urology · USNYU Langone Health · USRush University Medical Center · USSUNY Upstate Medical University · USThe University of Texas Health Science Center at San Antonio · USThe University of Texas Southwestern Medical Center · USThe Urology Center of Colorado · US

Funding

Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Scott Kopetz · 1985 to 2026
$290.8M
Women's Cancer Research ProgramP30CA014236 · NCI · DUKE UNIVERSITY · PI DONNA NIEDZWIECKI · 1985 to 2026
$174.8M
Viral VectorP30CA086862 · NCI · UNIVERSITY OF IOWA · PI Douglas Robert Spitz · 2000 to 2026
$70.0M
NCI NIH HHS P30 CA014236NCI NIH HHS P30 CA016672
6 · The paper itself

Abstract

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.

Indexed as

Antineoplastic AgentsUrinary Bladder NeoplasmsAdjuvants, ImmunologicAdministration, IntravesicalBCG VaccineFemaleHumansMaleNeoplasm InvasivenessNeoplasm Recurrence, LocalProspective StudiesAdjuvants, ImmunologicAntineoplastic AgentsBCG VaccineAntiadenovirus antibodyBladder cancerCompanion biomarkerGene therapyTreatment efficacy

Identifiers

PMID34933753
PMCPMC8891058
OpenAlexW4200516072

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.