Abstract
Background: VPM1002BC is a geneticallymodifiedMycobacteriumbovis bacillus CalmetteGuerin (BCG) strain with potentially improved immunogenicity and attenuation. Objective: To report on the efficacy, safety, tolerability and quality of life of intravesical VPM1002BC for the treatment of non-muscle-invasive bladder cancer (NMIBC) recurrence after conventional BCG therapy. Design, setting, and ...
Abstract
Background: VPM1002BC is a geneticallymodifiedMycobacteriumbovis bacillus CalmetteGuerin (BCG) strain with potentially improved immunogenicity and attenuation. Objective: To report on the efficacy, safety, tolerability and quality of life of intravesical VPM1002BC for the treatment of non-muscle-invasive bladder cancer (NMIBC) recurrence after conventional BCG therapy. Design, setting, and participants: We designed a phase 1/2 single-arm trial (NCT02371447). Patients with recurrent NMIBC after BCG induction +/- BCG maintenance therapy and intermediate to high risk for cancer progression were eligible. Intervention: Patients were scheduled for standard treatment of six weekly instillations with VPM1002BC followed by maintenance for 1 yr. Treatment was stopped in cases of recurrence. Outcome measurements and statistical analysis: The primary endpoint was defined as the recurrence-free rate (RFR) in the bladder 60 wk after trial registration. The sample size was calculated based on the assumption that >= 30% of the patientswould be without recurrence at 60 wk after registration. Results and limitations: After exclusion of two ineligible patients, 40 patients remained in the full analysis set. All treated tumours were of high grade and 27 patients (67.5%) presented with carcinoma in situ. The recurrence-free rate in the bladder at 60 wk after trial registration was 49.3% (95% confidence interval [CI] 32.1-64.4%) and remained at 47.4% (95% CI 30.4-62.6%] at 2 yr and 43.7% (95% CI 26.9-59.4%) at 3 yr after trial registration. At the same time, progression to muscle-invasive disease had occurred in three patients andmetastatic disease in four patients. Treatment-related grade 1, 2, and 3 adverse events (AEs) were observed in 14.3%, 54.8%, and 4.8% of the patients, respectively. No grade >= 4AEs occurred. Two of the 42 patients did not tolerate five ormore instillations during induction. Limitations include the single-armtrial design and the low number of patients for subgroup analysis. Conclusions: At 1 yr after treatment start, almost half of the patients remained recurrence-free after therapywithVPM100BC. The primary endpoint of the studywasmet and the therapy is safe and well tolerated. Patient summary: We conducted a trial of VPM100BC, a genetically modified bacillus Calmette-Guerin (BCG) strain for treatment of bladder cancer not invading the bladder muscle. At 1 year after the start of treatment, almost half of the patients with a recurrence after previous conventional BCG were free from non-muscle-invasive bladder cancer (NMIBC). The results are encouraging and VPM1002BC merits further evaluation in randomised studies for patients with NMIBC. (c) 2021 European Association of Urology. Published by Elsevier B.V. All rights reserved.
; Thalmann, George N. ; Lucca, Ilaria ; Kwiatkowski, Maciej ; Wirth, Grégory J. ; Strebel, Räto T. ; Engeler, Daniel ; Pedrazzini, Augusto ; Hüttenbrink, Clemens ; Schultze-Seemann, Wolfgang ; Torpai, Raimund ; Bubendorf, Lukas ; Wicki, Andreas 
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