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WASHINGTON -- The gene therapy nadofaragene firadenovec (Adstiladrin) continued to demonstrate clinical activity in patients with high-risk bladder cancer, researchers reported.

The long-term follow-up data came from a phase III study of patients with Bacillus Calmette-Guérin (BCG)-unresponsive non-muscle-invasive bladder cancer (NMIBC) with carcinoma in situ (CIS), with or without papillary tumors.

The data showed that of 55 patients who had achieved a complete response (CR) to the therapy at 3 months, 14 (25.5%) were still high-grade recurrence free at 3 years, according to Stephen A. Boorjian, MD, of the Mayo Clinic in Rochester, Minnesota, and colleagues, at the Society of Urologic Oncology (SUO) annual meeting.

The findings emphasize the importance of obtaining long-term data from novel therapies in order to set treatment expectations, he said.

Primary results, reported at the 2019 SUO meeting, demonstrated that the 55 patients who achieved a CR at 3 months represented 53.4% of 103 patients eligible for analysis. Here, Boorjian and colleagues reported that the long-term high-grade recurrence free results were:

• 40.8% (n=42 patients) at 6 months
• 35.0% (n=36) at 9 months
• 24.3% (n=25) at 1 year
• 19.4% (n=20) at 2 years
• 13.6% (n=14) at 3 years

In addition to the 3-year results, of those 55 patients who achieved a CR, the percentage who maintained that response was:

• 76.4% (n=42) at 6 months
• 65.5% (n=36) at 9 months
• 45.5% (n=25) at 12 months
• 36.4% (n=20) at 24 months

The median duration of CR was 9.7 months, and the probability of duration of CR for at least 36 months was 34.2%.

The cystectomy-free survival rate at 36 months was 53.8% (95% CI 43.3-63.1), and the 3-year overall survival rate was 90.4% (95% CI 82.3-94.9).

Nadofaragene firadenovec is an adenoviral vector-based product that the FDA in 2022 as the first gene therapy for the treatment of high-risk BCG-unresponsive NMIBC for adult patients with CIS, with or without papillary tumors.

The single-arm, open-label, multicenter enrolled 107 patients, 103 of whom met the protocol definition of BCG-unresponsive NMIBC and were included in an efficacy analysis.

Patients received nadofaragene 75 mL intravesical instillation (3 x 10¹¹ viral particles/mL) once every 3 months for up to 12 months (4 doses) or until unacceptable toxicity or recurrent high-grade NMIBC.

Per protocol, a five-site biopsy of the bladder was performed at 12 months, and patients who were high-grade recurrence free were offered continued treatment. The trial is ongoing with a planned 5-year treatment and monitoring phase.

The median age of the entire cohort of 107 patients was 72, 89% were male, and 99% had received at least two BCG courses before enrolling in the study.

Boorjian and colleagues reported that 3.9% (n=4) of patients experienced progression to muscle-invasive disease as documented by transurethral resection of bladder tumor at the time of high-grade recurrence. Two patients discontinued treatment due to adverse events (AE), including a grade 3 bladder spasm and a grade 2 instillation site discharge. Neither event was considered a serious AE.

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