Cystectomy-Free Survival Is Detailed With Nadofaragene

Bladder cancer with organs and cancerous cells: matthieu - stock.adobe.com

TREATMENT OF UNRESPONSIVE non–muscle-invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without Ta/T1 disease with nadofaragene firadenovec-vncg (Adstiladrin) was associated with a 66% Kaplan-Meier estimated probability of patients being alive and cystectomy- free at 60 months.¹ The findings were presented at the 25th Annual Meeting of the Society of Urologic Oncology (SUO) in Dallas, Texas.

Previously, findings presented at the SUO’s 2023 annual meeting showed that at the 36-month follow-up, 25.5% (14 of 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 or greater 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 with or without Ta/T1 disease, regardless of CR [complete response] status.”¹

“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 [were] the final pathologic data from patients who ultimately underwent radical cystectomy?” explained the study’s lead author, Vikram M. Narayan, MD, during a presentation of the data. Narayan is an assistant professor of urology at Emory University and the director of urological oncology at Grady Memorial Hospital in Atlanta, Georgia.

Patients with BCG-unresponsive NMIBC in the phase 3 open-label, multicenter CS-003 trial (NCT02773849) received 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. Reinduction 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.¹

A total of 107 patients were enrolled in the CIS with or without 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,” the authors wrote. Median patient age was 72 years, and 89% of the cohort was men. Median time from initial diagnosis of bladder cancer was 20 months. Regarding the number of prior BCG courses, 1 (1%) patient 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 plus 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 with or without Ta/T1 population, 63.9 months (95% CI, 58.3not estimable) in the CIS with or without Ta/T1 with CR cohort, and 11.3 months (95% CI, 9.3-29.7) in the CIS with or without 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 with or without Ta/T1 population, 65.5% (95% CI, 49.6%77.5%) in the CIS with or without Ta/T1 with CR cohort, and 16.0% (95% CI, 6.0%30.3%) in the CIS with or without Ta/T1 without CR cohort.

Of the 103 patients with CIS with or without 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%) patients 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.

“Our key finding was among patients who achieved a complete response at 3 months, about two-thirds 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…44 patients who ultimately underwent cystectomy. Only about 6 patients had muscle-invasive bladder cancer. That’s a key take-home [message] because of interest in how many of these patients progress,” Narayan said.

He concluded, “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: 25th Annual Meeting of the Society of Urologic Oncology. December 4-6, 2024. Dallas, TX. 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: 24th Annual Meeting of the Society of Urologic Oncology. November 28-December 1, 2023; Washington, DC. Abstract 164. Accessed November 30, 2024. https:// suo-abstracts.secure-platform.com/a/gallery/rounds/18/ details/2938