Dr Tyson on Factors Influencing the Selection of Nadofaragene Firadenovec in BCG-Unresponsive NMIBC

"[Which of these 3 agents to choose] is a tough question. The days for pembrolizumab monotherapy are coming to an end. Pembrolizumab monotherapy was a reasonable option, but now we have 2 intravesical therapies, which have demonstrated just as good or even slightly better efficacy in clinical trials, and certainly better tolerability."

Mark D. Tyson, II, MD, MPH, a urologic oncologist at Mayo Clinic, discusses factors informing the selection between nadofaragene firadenovec-vncg (Adstiladrin), nogapendekin alfa inbakicept-pml (Anktiva), and pembrolizumab (Keytruda) for the treatment of patients with Bacillus Calmette-Guérin (BCG)–unresponsive non–muscle-invasive bladder cancer (NMIBC).

According to the National Comprehensive Cancer Center guidelines, nadofaragene firadenovec, nogapendekin alfa, and pembrolizumab are all viable treatment options for patients with NMIBC who are not considered candidates for BCG or cystectomy. However, selecting between these therapies remains a challenge, Tyson begins.

Pembrolizumab monotherapy, which was once a reasonable option for patients unwilling to undergo cystectomy or further intravesical therapy, is becoming less relevant as intravesical therapies gain prominence, he asserts. Both nadofaragene firadenovec and nogapendekin alfa have demonstrated comparable or potentially superior efficacy vs pembrolizumab in clinical trials, with more favorable tolerability profiles due to the absence of systemic immune-related adverse effects, Tyson notes.

The choice between these intravesical agents involves logistical considerations, he continues. Nadofaragene firadenovec is administered once every 90 days as a monotherapy, whereas nogapendekin alfa is given in combination with BCG using the conventional induction and maintenance regimen, Tyson clarifies. If BCG supply is limited, nadofaragene firadenovec may be the preferred option, according to Tyson. Conversely, nogapendekin alfa demonstrated the highest complete response rate at 1 year in an FDA-defined population, which is approximately 2 times higher than that observed with nadofaragene firadenovec, Tyson adds. Although these response rates suggest a potential efficacy advantage with nadofaragene firadenovec over nogapendekin alfa, direct comparative studies have not been conducted, and definitive conclusions regarding superiority cannot yet be made, he states.

Given the absence of head-to-head trials, the decision between these agents ultimately comes down to individual patient preferences, treatment logistics, and institutional considerations, Tyson says. In clinical practice, both therapies are available, allowing for shared decision-making, he details. Some patients may prefer the less frequent dosing schedule of nadofaragene firadenovec, whereas others may be drawn to the response rates observed with nogapendekin alfa, Tyson concludes.