MP16-15: Intravesical electromotive mitomycin in patients with bacillus Calmette-Guérin-unresponsive primary high risk non-muscle invasive bladder cancer: an open label, single arm, phase II study
Friday, May 3, 2024 1:00 PM to 3:00 PM · 2 hr. (US/Central)
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Abstract
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Author Block
SAVINO MAURO DI STASI*, GIUSEPPE PALERMO, GIOVANNI CAPELLI, FRANCESCO PIO BIZZARRI, ELENA DI STASI, ANGELO TOTARO, SEYED KOOSHA MOOSAVI, MARCO RACIOPPI, ROME, Italy
Introduction
We investigated the effects of intravesical electromotive mitomycin (EMDA/MMC) in patients with primary high risk urothelial non-muscle invasive bladder cancer (NMIBC) who failed BCG therapy and were unfit or unwilling for cystectomy
Methods
From January 2006 to December 2018, patients with histologically confirmed BCG-unresponsive high risk NMIBC were enrolled. Following transurethral resection of bladder tumor (TURBT) and re-TURBT, patients were scheduled for an initial 6 weekly intravesical EMDA/MMC treatments, a further 6 weekly treatments for non-responders and 9 monthly treatments for responders. Patient follow-ups were done every 3 months for the first 2 years and every 6 months thereafter. Primary end-points were the complete response rate (absence of high-risk NMIBC or progressive disease) at 3 months for carcinoma in situ (Cis) and recurrence-free survival for fully resected papillary disease. Secondary end points include disease progression, overall survival and disease-specific survival. Analysis were done by intention-to-treat. Clinical-Trial.Gov, number NCT04311580
Results
From January 2006 to December 2018, 191 patients were enrolled and 89 (48 with Cis and 41 with papillary disease alone), according to the US FDA definition of BCG-unresponsive NMIBC, were included in the efficacy and safety analyses. Median follow-up of 40 months (IQR 58–27). Of 48 patients with Cis, 23 (47.9% [ 95% CI: 33.3-62.8], 26 (54.2% [39.2-68.6]), 19 (39.6% [25.8-54.7]), 12 (25% [13.6-39.6]), and 11 (22.9% [12.0-37.3]), had a complete response at 3, 6, 12, 18 and 24 months respectively. Of 41 patients with papillary disease alone, 38 (92.7% [ 95% CI: 80.1-98.5), 32 (78.1% [62.4-89.4), 29 (70.7 [54.5-63.9]), 20 (48.8% [32.9-54.9), and 17 (41.5% [26.3-57.9]) were recurrence-free 3, 6, 12, 18 and 24 months. Overall, patients with papillary disease alone than those with Cis alone had lower high grade recurrence (24.4% [12.4-40.3] vs 64.6% [49.5-77.4]; log-rank p=0.0002); progression (14.6% [5.6-29.2] vs 41.7[27.6-56.8]; p=0.0554); overall mortality (39 % [24.2-55.5] vs 68.7% [53.7-81,3]; p=0.9379); and disease-specific mortality (4.9% [0.6-16.5] vs 20.8[10.5-35]; p=0.1465]. Treatment-related adverse events were localised to the lower urinary tract
Conclusions
Intravesical EMDA/MMC is a safe and therapeutic option for patients with high risk NMIBC who fail BCG treatment. As BCG may induces delayed and longer cell mediated immunity after immunization, the FDA guidelines for patients with BCG failure should be reviewed
Source Of Funding
none
Author Block
SAVINO MAURO DI STASI*, GIUSEPPE PALERMO, GIOVANNI CAPELLI, FRANCESCO PIO BIZZARRI, ELENA DI STASI, ANGELO TOTARO, SEYED KOOSHA MOOSAVI, MARCO RACIOPPI, ROME, Italy
Introduction
We investigated the effects of intravesical electromotive mitomycin (EMDA/MMC) in patients with primary high risk urothelial non-muscle invasive bladder cancer (NMIBC) who failed BCG therapy and were unfit or unwilling for cystectomy
Methods
From January 2006 to December 2018, patients with histologically confirmed BCG-unresponsive high risk NMIBC were enrolled. Following transurethral resection of bladder tumor (TURBT) and re-TURBT, patients were scheduled for an initial 6 weekly intravesical EMDA/MMC treatments, a further 6 weekly treatments for non-responders and 9 monthly treatments for responders. Patient follow-ups were done every 3 months for the first 2 years and every 6 months thereafter. Primary end-points were the complete response rate (absence of high-risk NMIBC or progressive disease) at 3 months for carcinoma in situ (Cis) and recurrence-free survival for fully resected papillary disease. Secondary end points include disease progression, overall survival and disease-specific survival. Analysis were done by intention-to-treat. Clinical-Trial.Gov, number NCT04311580
Results
From January 2006 to December 2018, 191 patients were enrolled and 89 (48 with Cis and 41 with papillary disease alone), according to the US FDA definition of BCG-unresponsive NMIBC, were included in the efficacy and safety analyses. Median follow-up of 40 months (IQR 58–27). Of 48 patients with Cis, 23 (47.9% [ 95% CI: 33.3-62.8], 26 (54.2% [39.2-68.6]), 19 (39.6% [25.8-54.7]), 12 (25% [13.6-39.6]), and 11 (22.9% [12.0-37.3]), had a complete response at 3, 6, 12, 18 and 24 months respectively. Of 41 patients with papillary disease alone, 38 (92.7% [ 95% CI: 80.1-98.5), 32 (78.1% [62.4-89.4), 29 (70.7 [54.5-63.9]), 20 (48.8% [32.9-54.9), and 17 (41.5% [26.3-57.9]) were recurrence-free 3, 6, 12, 18 and 24 months. Overall, patients with papillary disease alone than those with Cis alone had lower high grade recurrence (24.4% [12.4-40.3] vs 64.6% [49.5-77.4]; log-rank p=0.0002); progression (14.6% [5.6-29.2] vs 41.7[27.6-56.8]; p=0.0554); overall mortality (39 % [24.2-55.5] vs 68.7% [53.7-81,3]; p=0.9379); and disease-specific mortality (4.9% [0.6-16.5] vs 20.8[10.5-35]; p=0.1465]. Treatment-related adverse events were localised to the lower urinary tract
Conclusions
Intravesical EMDA/MMC is a safe and therapeutic option for patients with high risk NMIBC who fail BCG treatment. As BCG may induces delayed and longer cell mediated immunity after immunization, the FDA guidelines for patients with BCG failure should be reviewed
Source Of Funding
none