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.
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.
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.
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
Bladder Cancer > Non-Muscle Invasive Bladder Cancer
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Presented By: Vikram M. Narayan
Vikram M. Narayan
Badrinath R. Konety
Ashish M. Kamat
Seth P. Lerner
Robert S. Svatek
Brant A. Inman
Colin P.N. Dinney