(UroToday.com) At the European Association of Urology 2021 annual meeting, Dr. Vikram M. Narayan, from Emory University presented results of several key subgroup analyses from the recently published trial assessing nadofaragene firadenovec in BCG-unresponsive NMIBC. The goals of treatment of NMIBC are to reduce recurrence and prevent progression, however, despite optimal treatment, ≥50% of patients who demonstrated an initial response to BCG will experience recurrence and progression and become BCG-unresponsive. With limited treatment options, there is an unmet medical need for local, effective, bladder-preserving treatment options.
Nadofaragene firadenovec is a non-replicating recombinant type-5 adenovirus vector-based gene therapy that delivers a copy of the human IFNα2b gene. Adenoviruses provide short-term, high but transient expression of the gene of interest in a relatively broad range of host cells. The Phase III trial of nadofaragene firadenovec for BCG unresponsive NMIBC was a multi-center study to investigate the safety and efficacy of intravesical nadofaragene firadenovec 75 mL once every 3 months in 157 patients with high-grade, BCG-unresponsive NMIBC. Cytology and cystoscopy (with biopsy if clinically indicated) were performed at 3, 6, and 9 months to evaluate for recurrence of high-grade disease. The protocol mandated a 5-site (dome, trigone, right and left lateral walls, posterior wall) biopsy at 12 months. Patients free from high-grade recurrence were eligible for retreatment at 3-month intervals while they remained high-grade recurrence free. The study met its primary endpoint with 53.4% of patients with CIS ±Ta/T1 achieving a complete response, all by 3 months, including 43.6% of these patients remaining free of high-grade recurrence at 15 months. This study was recently published in Lancet Oncology [1].
This multicenter, open-label phase III study enrolled patients into two cohorts: CIS ± Ta/T1 (n = 103) and high-grade Ta/T1 (High-Grade Ta or T1 without concomitant CIS; n=48).
The trial schema is as follows:
The subgroup analyses were based on the efficacy population for the following subgroups: age group (<70 or ≥70 years), sex, disease status at baseline (BCG-refractory or BCG-relapsed), prior lines of therapy (0 or ≥1), prior non-BCG regimens (≤3 or >3), prior courses of BCG (≤3 or >3).
At baseline, patients had median age of 70.8 years, 82.2% were male. The median prior lines of therapy were 3, non-BCG regimen was 0, and courses of BCG were 2. For both cohorts, the results of the subgroup analyses showed that there were no significant differences in response rates at 3 and 15 months between males and females, age groups, BCG-refractory vs. BCG-relapsed, ≤3 or >3 prior lines of therapy, 0 or ≥1 prior non-BCG regimens, and ≤3 or >3 prior courses of BCG. Additionally, there were no significant differences between the subgroups in duration of response, except in the CIS ± Ta/T1 cohort, where patients who had received ≤3 prior courses of BCG had significantly longer duration of response compared to patients who received >3 courses (12.7 vs. 5.0 months, p=0.02). Results from multivariable analysis confirmed that none of these baseline characteristics or prior therapy significantly contributed to response rates at 3 and 15 months or duration of response. These results are summarized in the following figure:
The conclusions from this presentation of key subgroup analyses of the nadofaragene firadenovec phase III trial are as follows:
- There were no significant differences in response rates between subgroups for both cohorts, except between patients in the CIS +/- Ta/T1 cohort who had received <=3 vs >3 prior courses of BCG at baseline
- Multivariable analyses confirmed no significant differences in response rates between all subgroups
- These results demonstrate the efficacy of nadofaragene firadenovec regardless of patient characteristics or prior treatment history
Presented by: Vikram Narayan, MD, Emory University School of Medicine, Dept. of Urology, Atlanta, GA
Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia, @zklaassen_md on Twitter during the 2021 European Association of Urology, EAU 2021- Virtual Meeting, July 8-12, 2021.
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