High cystectomy-free survival seen with nadofaragene treatment in NMIBC

Treatment of unresponsive non–muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) +/- Ta/T1 disease with nadofaragene firadenovec-vncg (Adstiladrin) was associated with a 66% Kaplan-Meier-estimated probability of being alive and cystectomy free at 60 months.¹

The findings were presented at the Society of Urologic Oncology (SUO) 25th Annual Meeting in Dallas, Texas.

Findings presented at the SUO 24th Annual Meeting showed that at 36 months’ follow-up, 25.5% (14/55) of the patients who had a complete response at 3 months remained high-grade recurrence free. Per Kaplan-Meier estimate, the probability of reaching a ≥36-month complete response duration was 34.2%. The median complete response duration was 9.7 months.²

For the current study, the investigators sought “to evaluate whether nadofaragene firadenovec would enable participants to avoid cystectomy without compromising the window of cure in those with CIS ± Ta/T1 disease, regardless of CR status.”

Vikram M. Narayan, MD

“What we were interested in understanding was in patients who were on that trial, how many ultimately proceeded to undergo cystectomy, what were the characteristics of those patients, and what was the final pathologic data from patients who ultimately underwent radical cystectomy?” explained study author Vikram Narayan, MD, to Urology Times. Narayan is an assistant professor of urology at Emory University and the director of urological oncology at Grady Memorial Hospital in Atlanta, Georgia.

The phase 3 open-label, multicenter CS-003 enrolled patients with BCG-unresponsive NMIBC to receive a single dose of nadofaragene firadenovec, “with repeat dosing every 3 months for up to 4 doses in the absence of high-grade recurrence,” the authors wrote in their poster. After the initial 12 months of treatment, patients could continue to receive nadofaragene firadenovec every 3 months for up to 5 years total at physician discretion and if no high-grade recurrence was present. Re-induction was not given to patients who experienced high-grade recurrence at any time; these patients did not receive further treatment and were instead followed for cystectomy and survival outcomes for up to 5 years following the first instillation of nadofaragene firadenovec. The investigators recorded incidence of cystectomy as well as cystectomy-free survival.

A total of 107 patients were enrolled in the CIS +/- Ta/T1 cohort and received at least 1 dose of nadofaragene firadenovec; 103 patients “met the inclusion criteria of BCG-unresponsive NMIBC and were included in the efficacy analysis set,” wrote the authors. Median patient age was 72 years, and 89% of the cohort was male. Median time from initial diagnosis of bladder cancer was 20 months. Regarding number of prior BCG courses, 1 (1%) had received 1 course, 45 (42%) patients had received 2 courses, and 61 (57%) patients had received at least 3 courses. At study entry, 81 (76%) patients had CIS only, 21 (20%) had Ta + CIS, and 5 (5%) had T1 plus CIS.

The investigators reported a median Kaplan-Meier-estimated duration of cystectomy-free survival of 47.9 months (95% CI, 27.3-60.7) in the overall CIS +/- Ta/T1 population, 63.9 months (95% CI, 58.3-NE) in the CIS +/- Ta/T1 with CR cohort, and 11.3 months (95% CI, 9.3-29.7) in the CIS +/- Ta/T1 without CR cohort. Further, Kaplan-Meier probability of cystectomy-free survival for at least 60 months was 43.2% (95% CI, 32.2-53.7) in the overall CIS +/- Ta/T1 population, 65.5% (95% CI, 49.6-77.5) in the CIS +/- Ta/T1 with CR cohort, and 16.0% (95% CI, 6.0-30.3) in the CIS +/- Ta/T1 without CR cohort.

Of the 103 patients with CIS +/- Ta/T1 disease, a total of 44 (42.7%) underwent cystectomy. This included 15 (14.6%) patients who achieved a CR at 3 months and 29 (28.2%) patients who did not. In addition, in the cohort of 103 patients, 37 (35.9%) who underwent cystectomy had pathology data available. In this group, 28 (75.7%) had NMIBC at cystectomy; 8 patients had a CR and 20 did not. Six (16.2%) had MIBC at cystectomy; 3 patients had a CR and 3 did not. Three (8.1%) patients were pT0 at cystectomy; 1 patient had a CR and 2 did not.

“Our key finding was among patients who achieved a complete response at 3 months, about 2/3 of patients were able to be cystectomy-free at 60 months. This is a significant number of patients, obviously, who were able to avoid cystectomy. Among those who did undergo cystectomy, we had pathology for about 37 of the, I think, 44 patients who ultimately underwent cystectomy. Only about 6 patients had muscle-invasive bladder cancer. That's a key take-home as well, because of interest is how many of these patients progress,” Narayan told Urology Times.

He added, “Overall, the take-home message is that in patients with BCG-unresponsive non–muscle invasive bladder cancer, you can consider nadofaragene as an option among those that are available for treating these patients.”

REFERENCES

1. Narayan VM, Boorjian SA, Crispen PL, et al. Incidence and pathologic outcomes of cystectomy in patients with bacillus Calmette-Guérin-unresponsive non–muscle-invasive bladder cancer with carcinoma in situ following treatment with nadofaragene firadenovec-vncg. Presented at: Society of Urologic Oncology 25th Annual Meeting. December 4-6, 2024. Dallas, Texas. Abstract 215. Accessed December 9, 2024. https://suo-abstracts.secure-platform.com/a/gallery/rounds/21/details/4002

2. Boorjian SA, Narayan VM, Konety BR, et al. Efficacy of intravesical nadofaragene firadenovec-vncg for patients with bacillus Calmette-Guérin-unresponsive carcinoma in situ of the bladder: 36-month follow-up from a phase 3 trial. Presented at: 2023 Society of Urologic Oncology Annual Meeting. November 28 – December 1, 2023; Washington, DC. Abstract 164.