SUO 2020: Low Rate of Cystectomy and Delayed Median Time to Cystectomy Among Patients Who Achieved Complete Response with Nadofaragene Firadenovec

(UroToday.com) Most patients with newly diagnosed bladder cancer have non-muscle invasive disease (NMIBC). For patients with intermediate or high-risk NMIBC and those with carcinoma in situ (CIS), adjuvant treatment with Bacillus Calmette Guerin (BCG) is recommended by many guideline bodies due to proven benefits in disease recurrence. For patients who become BCG-unresponsive, there have been very limited options for these patients for many years. Radical cystectomy has remained the gold standard through numerous approaches including intravesical and systemic therapies have been investigated. Recently, pembrolizumab has been approved for this indication and, as of a recent publication of phase III data this week, nadofaragene firadenovec, a novel intravesical gene-mediated therapy that delivers the human IFNα2b gene resulting in sustained IFNα2b expression, has proven efficacy. In the primary outcome analysis, 53% of patients with CIS +/- Ta/T1 disease achieved complete response, with 44% of these remaining free of high-grade recurrence at 15 months.

In a poster presentation at the Society of Urologic Oncology meeting, Dr. Vikram Narayan and colleagues examined a key secondary outcome of this study, the incidence, and timing of cystectomy among patients receiving nadofaragene firadenovec.

To briefly recap the study design, this phase III open-label, single-arm study enrolled patients in two cohorts: first, CIS with or without papillary Ta/T1 disease (n=103) and, second, high-grade Ta/T1 without concomitant CIS (n=48).

Nadofaragene firadenovec was administered once every three months for up to 4 doses. Surveillance was performed with protocol mandated biopsy (dome, trigone, right and left lateral walls, and posterior wall) at 12 months. For this analysis, the authors used a 15-month data cut off.

Among 151 patients enrolled, 40 patients (26.5%) underwent cystectomy: 30 (29%) of patients in the CIS +/- Ta/T1 disease and 10 (21%) of patients in the HG-Ta/T1 without CIS cohort. Median time to cystectomy among these patients was 8.87 and 8.31 months respectively.

As may be expected, patients who achieved complete response had significantly longer median time to cystectomy than those who failed to achieve complete response: 11.4 vs 6.4 months, respectively, in the CIS +/- Ta/T1 cohort (p=0.04) and 12.4 vs 5.3 months, respectively in the HG-Ta/T1 without CIS cohort (p=0.01).

Among all patients, cystectomy free survival was 73.5% at 12-months and 64.5% at 24-months.

The authors conclude that these rates of cystectomy-free survival are better than historical controls with other salvage therapies.

Presented by: Vikram M. Narayan, MD, Assistant Professor of Urology, Department of Urology, Emory University School of Medicine, Director of Urological Oncology, Grady Memorial Hospital, Atlanta, GA

Written by: Christopher J.D. Wallis, MD, Ph.D., Instructor in Urology, Vanderbilt University Medical Center, Nashville, Tennessee @WallisCJD on Twitter at the 2020 Society of Urologic Oncology Annual Meeting – December 2-5, 2020 – Washington, DC

Related Content:

SUO 2020: Subgroup Analyses of the Phase 3 Study of Intravesical Nadofaragene Firadenovec in Patients with High-Grade, Bacillus Calmette Guerin (BCG)-Unresponsive Non Muscle Invasive Bladder Cancer (NMIBC)

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