(UroToday.com) The 2024 European Association of Urology (EAU) annual meeting featured a session on non-muscle invasive bladder cancer, and a presentation by Dr. Colin Dinney discussing 36 month follow-up from the phase 3 trial assessing the efficacy of intravesical nadofaragene firadenovec-vncg for patients with BCG-unresponsive non-muscle-invasive bladder cancer.
BCG is the first-line standard of care treatment for patients with high-risk non-muscle invasive bladder cancer, however, some studies suggest that more than 50% of patients who respond to initial BCG treatment will experience disease recurrence or progression during long-term follow-up, with many patients having disease that is re-categorized to BCG-unresponsive. Local bladder-preserving treatment options are needed for patients with BCG-unresponsive non-muscle-invasive bladder cancer. Nadofaragene firadenovec-vncg, a non-replicating adenovirus vector-based gene therapy, is approved by the US FDA for patients with BCG-unresponsive non-muscle-invasive bladder cancer with carcinoma in situ (CIS) with/without papillary tumors (±Ta/T1). The primary endpoint of the open-label, multicenter, phase 3 study (NCT02773849) of nadofaragene firadenovec was met, as 53.4% (95% CI 43.3-63.3) of patients with CIS ± Ta/T1 achieved complete response at 3 months.1 At the 2024 EAU annual meeting, Dr. Dinney presented 36-month follow-up results from this study.
Patients with BCG-unresponsive non-muscle-invasive bladder cancer (n = 157) were enrolled, of which 107 and 50 patients were in the CIS ± Ta/T1 (CIS) and Ta/T1 without CIS (papillary disease) cohorts, respectively. Efficacy analysis included 103 and 48 patients in the CIS and papillary disease cohorts, respectively, who met the protocol definition of BCG-unresponsive non-muscle-invasive bladder cancer. Patients received nadofaragene firadenovec once every 3 months with cystoscopy and cytology assessments. Biopsies were taken at 12 months and patients who remained high-grade recurrence-free were offered continued treatment at the investigator’s discretion. The trial design is as follows:
All patients completed the 36-month visit or discontinued by September 9, 2021, and the mean duration of follow-up was 42.6 (SD 12.2) months. There were 13/107 (12.1%) and 10/50 (20.0%) patients in the CIS and papillary disease cohorts that received nadofaragene firadenovec at Month 36, respectively. Among patients with CIS who achieved complete response at 3 months (53.4%), 14/55 (25.5%) remained high-grade recurrence-free at 36 months:
Among patients with high-grade Ta/T1 who achieved complete response at 3 months (72.9%), 11/35 (31.4%) remained high-grade recurrence-free at 36 months:
The median duration of complete response was 9.7 (95% CI 9.2-24.0) months, and the probability of duration of complete response for at least 36 months was 34.2% (95% CI 21.6-47.1%):
In the CIS ± Ta/T1 cohort, the Kaplan-Meier estimated median duration of high-grade recurrence free survival was 6.0 months (95% CI 3.4-8.3), and in the high-grade Ta/T1 cohort was 12.4 months (95% CI 6.7-20.3):
Four (3.9%) patients with CIS and 1 (2.1%) patient with papillary disease experienced progression to muscle-invasive disease documented by transurethral resection of bladder tumor at the time of high-grade recurrence as collected in the electronic case report form. Overall, 54 patients (35.8%) underwent cystectomy, with a Kaplan-Meier-estimated cystectomy-free survival rate at Month 36 of 53.8% (95% CI 43.3-63.1) and 63.6% (95% CI 48.0-75.6) in the CIS and papillary disease cohorts, respectively. The Kaplan-Meier-estimated overall survival rate at Month 36 was 90.4% (95% CI 82.3-94.9) and 91.3% (95% CI 78.5-96.7) in the CIS and papillary disease cohorts, respectively.
Three participants discontinued therapy because of adverse events. In the CIS cohort, one patient discontinued secondary to grade 3 bladder spasm, and one patient discontinued because of grade 2 instillation site discharge. In the high-grade Ta/T1 cohort, one participant discontinued because of grade 2 benign neoplasm of the bladder. No events leading to discontinuation were considered serious adverse events. There were no new safety signals seen during long-term follow-up.
Dr. Dinney concluded his presentation discussing 36 month follow-up from the phase 3 trial assessing the efficacy of intravesical nadofaragene firadenovec-vncg for patients with BCG-unresponsive non-muscle-invasive bladder cancer with the following conclusions:
- Intravesical nadofaragene firadenovec, administered once every 3 months, demonstrated a durable sustained complete response of 9.7 months
- Approximately 25% of participants with BCG-unresponsive CIS ± Ta/T1 papillary disease who achieved complete response remained high grade recurrence free by 36 months
- In participants with high-grade Ta/T1 papillary disease, 31% of participants who were high grade recurrence free at 3 months remained at 36 months
- There were no new safety signals seen through 36 months of follow-up
- Nadofaragene firadenovec is a novel and safe intravesical treatment option for BCG-unresponsive non-muscle-invasive bladder cancer
Presented by: Professor Colin P. Dinney, MD, Chairman, MD Anderson Cancer Center, Houston, Texas
Written by: Zachary Klaassen, MD, MSc - Urologic Oncologist, Associate Professor of Urology, Georgia Cancer Center, WellStar MCG Health, @zklaassen_md on Twitter during the 2024 European Association of Urology (EAU) annual congress, Paris, France, April 5th - April 8th, 2024
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