Introduction:
Patients with bacillus Calmette-Guérin (BCG)-unresponsive high-grade (HG) non-muscle invasive bladder cancer (NMIBC) are at significant risk for disease progression. While cystectomy can be curative in this setting, it is associated with high perioperative morbidity, a risk of mortality and decreased quality-of-life. Thus, most patients with BCG-unresponsive NMIBC either decline or are deemed inelibile for cystectomy. There is an unmet medical need for effective bladder-preserving treatment options.
Nadofaragene firadenovec is a non-replicating recombinant adenovirus vector-based gene therapy. This Phase 3 study assessed its safety and efficacy in 157 patients with HG, BCG-unresponsive NMIBC. The study met its primary endpoint with 53.4% of patients with CIS ± Ta/T1 achieving a complete response (CR), all by 3 months. 43.6% of these patients remained free of HG recurrence at 15 months.
Herein we report the incidence of and time to cystectomy, a key secondary objective of the Phase 3 study.
Methods:
The multicenter, open-label Phase 3 study enrolled patients into two cohorts: CIS ± Ta/T1 (carcinoma in situ with or without high-grade Ta or T1) and HG Ta/T1 (HG Ta or T1 without concomitant CIS) with 103 and 48 patients, respectively, included in the efficacy analysis.
Nadofaragene (3x1011 vp/mL [75 mL]) was administered once every 3 months for up 4 doses, with additional dosing at the investigator’s discretion. The protocol mandated a 5-site (dome, trigone, right and left lateral walls, posterior wall) biopsy at 12 months.
This analysis was based on the data cut-off at 12 months.
Results:
A total of 40 (26.5%) patients underwent cystectomy, including 30 (29.1%) in the CIS ± Ta/T1 cohort with median time to cystectomy being 8.87 months, and 10 (20.8%) in the HG Ta/T1 cohort with median time to cystectomy being 8.31 months.
Within the CIS ± Ta/T1 cohort, patients who achieved CR had significantly longer median time to cystectomy compared those who did not (p=0.0432; 11.35 vs 6.36 months, respectively).
Within the HG Ta/T1 cohort, patients who were free of HG recurrence at month 3 also had significantly longer median time to cystectomy versus those with HG recurrence at 3 months (p=0.0095; 12.42 vs 5.31 months, respectively).
The cystectomy-free survival among all treated patients was 64·5% at 24 months and was similar between the cohorts.
Conclusion:
Of patients with HG BCG-unresponsive NMIBC treated nadofaragene firadenovec, 73.5% remained free of cystectomy at 12 months.
The rate of cystectomy is lower with nadofaragene firadenovec compared to historical data of 30-50% with other salvage intravesical therapies.
Nadofaragene firadenovec is an effective bladder-sparing treatment for patients with HG BCG-unresponsive NMIBC as demonstrated by lower rate of cystectomy and longer median time to cystectomy.
Clinical trial information: NCT02773849
Funding: FKD Therapies Oy, Finland
Image(s) (click to enlarge):
LOW RATE OF CYSTECTOMY AND DELAYED MEDIAN TIME TO CYSTECTOMY AMONG PATIENTS WHO ACHIEVED COMPLETE RESPONSE WITH NADOFARAGENE FIRADENOVEC
Category
Bladder Cancer > Non-Muscle Invasive Bladder Cancer
Description
Poster #38
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Presented By: Vikram M. Narayan
Authors:
Vikram M. Narayan
Stephen Boorjian
Mehrdad Alemozaffer
Badrinath R. Konety
Leonard Gomella
Ashish M. Kamat
Seth P. Lerner
Robert S. Svatek
Lawrence Karsh
Daniel Canter
Yair Lotan
Brant A. Inman
Mindy Yang
Viviana Garcia-Horton
David Sawutz
Nigel Parker
Colin P.N. Dinney