TY - JOUR
T1 - International Bladder Cancer Group Consensus Statement on Clinical Trial Design for Patients with Bacillus Calmette-Guérin–exposed High-risk Non–muscle-invasive Bladder Cancer
AU - Roumiguié, Mathieu
AU - Kamat, Ashish M.
AU - Bivalacqua, Trinity J.
AU - Lerner, Seth P.
AU - Kassouf, Wassim
AU - Böhle, Andreas
AU - Brausi, Maurizio
AU - Buckley, Roger
AU - Persad, Raj
AU - Colombel, Marc
AU - Lamm, Donald
AU - Palou-Redorta, Juan
AU - Soloway, Mark
AU - Brothers, Ken
AU - Steinberg, Gary
AU - Lotan, Yair
AU - Sylvester, Richard
AU - Alfred Witjes, J.
AU - Black, Peter C.
N1 - Funding Information:
Financial disclosures: Mathieu Roumiguié certifies that all conflicts of interest, including specific financial interests and relationships and affiliations relevant to the subject matter or materials discussed in the manuscript (eg, employment/affiliation, grants or funding, consultancies, honoraria, stock ownership or options, expert testimony, royalties, or patents filed, received, or pending), are the following: Mathieu Roumiguié has been a consultant for Astellas Pharma, AstraZeneca, Pfizer, Janssen Oncology, Bayer, Ferring, and Pierre Fabre. Peter C. Black has been a consultant for AbbVie, Astellas Pharma, EMD-Serono, Pfizer, Janssen Oncology, Bayer, Merck, Sanofi Canada, Biosyent, Ferring, Roche Canada, MDxHealth, AstraZeneca, UroGen Pharma, Bristol-Myers Squibb, Fergene, Prokarium, Protara, QED, STIMIT, Theralase, and Verity; has received research funding from iProgen; and shares a patent with Decipher Biosciences. Richard Sylvester is a member of the EAU NMIBC guidelines panel. Ashish M. Kamat has been a consultant for Arquer Diagnostics, Asieris, Biological Dynamics, Bristol-Myers Squibb, CG Oncology, H3 Biomedicine/Eisai, Engene, FerGene, Imagin Medical, Janssen, Medac, Merck, Photocure, ProTara, Seattle Genetics, Sesen Bio, Theralase, US Biotest, UroGen Inc., Roche, and TMC Innovation; has received research funding from Adolor, BMS, FKD Industries, FerGene, Heat Biologics, Merck, Photocure, SWOG, NIH/GU Spore, AIBCCR, Janssen (+Taris), and Seattle Genetics; shares a patent CyPRIT; and is board member of the International Bladder Cancer Group. Gary Steinberg is a member of clinical trial protocol committees for Merck, BMS, Janssen, CG Oncology, Pfizer, PhotoCure, Fidia, Seagen, and Protara; has been a scientific advisor/consultant for Heat Biologics, CG Oncology, PhotoCure, Merck, Roche/Genentech, Ciclomed, Taris Biomedical (now Janssen), MDxHealth, Fidia Farmaceutici, UroGen, Ferring, Aduro, Boston Scientific, Bristol-Myers Squibb, AstraZeneca, Pfizer, Janssen, Epivax Therapeutics, Natera, FKD, EnGene Bio, Sesen Bio, BioCanCell (now Archiano), Nucleix, Ipsen, Combat Medical, Astellas, Fergene, Dendreon, AbbVie, Seattle Genetics, Verity Pharmaceuticals, Regeneron, STIMIT, and Vyriad; and has equity stock/options in Epivax Therapeutics and UroGen. Wassim Kassouf has been a scientific advisor or consultant for Sesen Bio, Roche, Janssen, Merck, Ferring, BMS, AbbVie, and Astellas; has received research funding for clinical trials from Sesen Bio, Roche, Theralase, BMS, and Janssen; and led the CUA 2021 NMIBC guidelines. Yair Lotan has been a scientific advisor or consultant for Nanorobotics, C2i Genomics, Photocure, AstraZeneca, Merck, Fergene, AbbVie, Cleveland Diagnostics, Nucleix, Ambu, Seattle Genetics, Hitachi, Ferring Research, Verity Pharmaceuticals, Virtuoso Surgical, Nanorobot, Stimit, Abbott, Cepheid, Pacific Edge, FKD, MDxHealth, Biocancell, GenomeDx Biosciences, Storz, Vessi Medical, CAPs Medical, Radera, Synergo, BMS, UroGen, and Zymo; and has stock/options in Vessi, CAPs Medical, C2i Genomics, and Nanorobot. Seth P. Lerner has been a scientific advisor or consultant for Aura Bioscience, BMS, C2i Genomics, FerGene, Genentech, Merck, Pfizer/EMD Serono, Stimit, UroGen, Vaxiion, and Verity; has received research funding for clinical trials from Endo, FKD, JBL (SWOG), Genentech (SWOG), QED Therapeutics, UroGen, Vaxiion, and Viventia; shares a patent for a TCGA classifier; and has received honoraria from Annenberg, Clinical Care Options, Grand Rounds Urology, Ology, and UroToday. Roger Buckley has been a scientific advisor or consultant for Tersera, Astellas, AbbVie, Ferring, and BMS. Trinity J. Bivalacqua has been a scientific advisor or consultant for Biogenesis and Janssen and has received research funding for clinical trials from CG Oncology, Merck, and Aura. Maurizio Brausi has participated in steering committees for Arquer and Physion. Donald Lamm has research projects in bladder cancer sponsored by CG Oncology and US Biotest. Juan Palou-Redorta has been a scientific advisor or consultant for Pfizer, AstraZeneca, Merck, Janssen, BMS, Combat BRS, Olympus, Sanofi Pasteur, and Cepheid; and has received research funding for clinical trials from Cepheid, Combat RS, Arquer Diagnosis, and IDL Biotech AB. Raj Persad, Ken Brothers, Marc Colombel, J. Alfred Witjes, Mark Soloway, and Andreas Böhle have nothing to disclose.
Publisher Copyright:
© 2021 European Association of Urology
PY - 2022/7
Y1 - 2022/7
N2 - Context: A large proportion of patients with non–muscle-invasive bladder cancer (NMIBC) fall in the gap between bacillus Calmette-Guérin (BCG)-naïve and BCG-unresponsive disease. As multiple therapeutic agents move into this gray area, there is a critical need to define the disease state and establish recommendations for optimal trial design. Objective: To develop a consensus on optimal trial design for patients with BCG-exposed NMIBC, defined as high-grade recurrence after BCG treatment that does not meet the criteria for BCG-unresponsive disease. Evidence acquisition: We conducted a literature review using the Cochrane Library, Medline, and Embase and a review of clinical trials in ClinicalTrials.gov as a basis to generate consensus recommendations for clinical trial design in BCG-exposed NMIBC. Evidence synthesis: BCG-exposed NMIBC encompasses BCG resistance (presence of high-grade Ta or carcinoma in situ [CIS] at 3-mo evaluation after induction BCG) and delayed relapse. Randomized controlled trials are required to compare experimental therapies to a control arm receiving additional BCG, although ongoing BCG shortages may impact our ability to follow an optimal trial design. A placebo should be used in combination with BCG if the treatment arm includes BCG plus a study drug. Trials will either need to separate patients with and without CIS into two cohorts, or stratify by the presence of CIS at the time of randomization. If two cohorts are used, the primary endpoint for CIS patients should be complete response within a predetermined time. The primary endpoint in a cohort with Ta/T1 only, or if a single combined cohort is used, should be the duration of event-free survival. Suggested efficacy thresholds and corresponding sample sizes are provided. Conclusions: The International Bladder Cancer Group has developed recommendations regarding definitions, endpoints, and clinical trial design for BCG-exposed NMIBC to encourage uniformity among studies in this disease state. Patient summary: Our consensus provides a precise definition of the disease state for bladder cancer not invading the bladder muscle and exposed to bacillus Calmette-Guérin (BCG) treatment. Clear guidance for conducting optimal clinical trials in this disease setting was established and we believe that this will promote further progress in this field.
AB - Context: A large proportion of patients with non–muscle-invasive bladder cancer (NMIBC) fall in the gap between bacillus Calmette-Guérin (BCG)-naïve and BCG-unresponsive disease. As multiple therapeutic agents move into this gray area, there is a critical need to define the disease state and establish recommendations for optimal trial design. Objective: To develop a consensus on optimal trial design for patients with BCG-exposed NMIBC, defined as high-grade recurrence after BCG treatment that does not meet the criteria for BCG-unresponsive disease. Evidence acquisition: We conducted a literature review using the Cochrane Library, Medline, and Embase and a review of clinical trials in ClinicalTrials.gov as a basis to generate consensus recommendations for clinical trial design in BCG-exposed NMIBC. Evidence synthesis: BCG-exposed NMIBC encompasses BCG resistance (presence of high-grade Ta or carcinoma in situ [CIS] at 3-mo evaluation after induction BCG) and delayed relapse. Randomized controlled trials are required to compare experimental therapies to a control arm receiving additional BCG, although ongoing BCG shortages may impact our ability to follow an optimal trial design. A placebo should be used in combination with BCG if the treatment arm includes BCG plus a study drug. Trials will either need to separate patients with and without CIS into two cohorts, or stratify by the presence of CIS at the time of randomization. If two cohorts are used, the primary endpoint for CIS patients should be complete response within a predetermined time. The primary endpoint in a cohort with Ta/T1 only, or if a single combined cohort is used, should be the duration of event-free survival. Suggested efficacy thresholds and corresponding sample sizes are provided. Conclusions: The International Bladder Cancer Group has developed recommendations regarding definitions, endpoints, and clinical trial design for BCG-exposed NMIBC to encourage uniformity among studies in this disease state. Patient summary: Our consensus provides a precise definition of the disease state for bladder cancer not invading the bladder muscle and exposed to bacillus Calmette-Guérin (BCG) treatment. Clear guidance for conducting optimal clinical trials in this disease setting was established and we believe that this will promote further progress in this field.
KW - Bacillus Calmette-Guérin
KW - Clinical trials
KW - Intravesical therapy
KW - Non–muscle-invasive bladder cancer
KW - Risk stratification
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U2 - 10.1016/j.eururo.2021.12.005
DO - 10.1016/j.eururo.2021.12.005
M3 - Review article
C2 - 34955291
AN - SCOPUS:85121835431
SN - 0302-2838
VL - 82
SP - 34
EP - 46
JO - European urology
JF - European urology
IS - 1
ER -