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Nadofaragene for High-Grade BCG-Unresponsive NMIBC

Urothelial carcinoma.

Intravesical nadofaragene firadenovec is an effective and well-tolerated treatment for high-grade nonmuscle invasive bladder cancer (NMIBC) carcinoma in situ (CIS) that does not respond to intravesical Bacillus Calmette-Guerin (BCG), according to results of a multicenter, open-label phase 3 trial presented this past Friday at the 2020 Genitourinary Cancers Symposium.

For patients with BCG-unresponsive NMIBC, there is a substantial risk of disease recurrence and progression. Cystectomy is often a curative treatment, but many patients are either unwilling or unable to undergo this surgery, and there is a lack of effective salvage intravesical therapies for patients with high-risk, BCG-unresponsive disease.

The study enrolled 157 patients with BCG-unresponsive NMIBC, all of whom were included in the safety analysis, while efficacy was evaluated in 151 patients. Patients were given nadofaragene firadenovec, a novel intravesical gene-mediated therapy that delivers the human IFNα2b gene, once every three months for up to four doses in the initial 12 months, with additional dosing at the investigators' discretion. The study's primary end point was complete response at any time among patients with CIS.

Fifty-five of the 103 patients with CIS (53.4%) achieved complete response, all by the third month after treatment. Of these patients, 45.5% had not experienced high-grade recurrence at the end of one year, as confirmed on protocol-mandated biopsy. For patients with high-grade Ta/T1 cancer without CIS, 72.9% were recurrence free at three months, as were 43.8% at 12 months.

Treatment-emergent adverse events were largely transient and included instillation site discharge (33.1%), fatigue (23.6%), bladder spasm (19.7%), micturition urgency (17.8%), and hematuria (16.6%). Two grade 4 treatment-emergent adverse events occurred (sepsis and anaphylactic reaction); however, neither were related to the study drug. There were no grade 5 treatment-emergent adverse events.

"Nadofaragene achieved complete response in 53.4% of patients with BCG-unresponsive CIS and was well tolerated. Responses were noted early and remained durable to one year," conclude authors Stephen A. Boorjian, MD, Vice Chair of Urology Research at Mayo Clinic, Rochester, Minnesota, and Colin P.N. Dinney, MD, Chairman of Urology at the University of Texas MD Anderson Cancer Center, Houston, Texas. "These data represent a potentially significant management advancement for a historically difficult-to-treat disease state."

For More Information

Boorjian SA & Dinney CPN (2020). Safety and efficacy of intravesical nadofaragene firadenovec for patients with high-grade, BCG unresponsive nonmuscle invasive bladder cancer (NMIBC): results from a phase III trial. J Clin Oncol (Genitourinary Cancers Symposium Abstracts), 38(suppl_6). Abstract 442.

Image credit: Nephron. Licensed under CC BY-SA 3.0

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