Abstract 2691: A randomized Phase III study comparing the efficacy of Bacillus Calmette Guérin strain Tice versus Connaught for immunotherapy of non-muscle invasive bladder cancer

Abstract

Abstract Introduction: For almost forty years now, adjuvant immunotherapy with intravesical Bacillus Calmette Guérin (BCG) is standard of care in the treatment of non-muscle invasive bladder cancer (NMIBC). The question whether the choice of the different available BCG strains used for treatment influences treatment outcome is still under debate. We report on a randomized phase III study comparing the two most commonly used strains in Europe and the USA. Patients and Methods: This study was performed under approval of the Cantonal Ethical Committee of Bern, Switzerland, to evaluate recurrence free survival in patients treated with BCG as the primary end-point. Between 1998 and 2010 149 patients (n=149) were recruited. Patients underwent transurethral resection of all visible bladder tumors or random bladder biopsies in case of a solely positive bladder wash cytology. TaG3 and T1G3 tumors underwent a second resection to confirm non-muscle invasive disease. Two to 15 days after surgery, patients were either randomized to receive six weekly intravesical instillations with 2-8x108 CFU OncoTice ® (BCG Tice) or 6.6-19.2 x108 CFU ImmuCyst ® (BCG Connaught) dissolved in 50 ml of saline according to manufacturers recommendations. Patients were followed in 3-monthly intervals for 3yrs, then in 6-monthly intervals by cystoscopy and bladder wash cytology. Relapses were confirmed by histology after transurethral surgery. Cox regression analysis and Log rank tests served for statistical analysis. Results: Gender, age, tumor stage and grade were well balanced between the two treatment arms (p=0.38). Median follow up was 25 months (range: 0.3-136). Side effects did not differ between the two treatment arms (p=0.42). Age and gender did not have an impact on treatment response (p=0.71). Five year recurrence-free survival for all patients was 61%. Patients treated with Connaught had significantly less recurrences than patients treated with OncoTice (p<0.002). Five year recurrence-free survival was 75% and 46% for Connaught and Tice treated patients, respectively. Median recurrence-free survival was 28 months (range: 0.6-136) for Connaught and 22 months (range: 0.3-122) for Tice treated patients. Progression-free and overall survivals were not significantly different between the two treatment arms. Conclusions: The choice of the BCG strain impacts on treatment outcome and favors the use of BCG Connaught over Tice in the treatment of NMIBC. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2691. doi:1538-7445.AM2012-2691