Nadofaragene firadenovec in high-risk Bacillus Calmette Guérin unresponsive non-muscle invasive bladder cancer: a profile of its use

Nadofaragene firadenovec (Adstiladrin (R)) is an important bladder-sparing option in the treatment of patients with high-risk Bacillus Calmette Guerin (BCG)-unresponsive non-muscle invasive bladder cancer (NMIBC). Radical cystectomy is the recommended treatment in these patients; however, many are ineligible or refuse to undergo this major procedure and other options are limited. Intravesical nadofaragene firadenovec, a replication-deficient adenovirus-based gene therapy that causes localized expression of interferon (IFN) alpha 2b in the bladder, is approved in the USA for the treatment of adults with high-risk BCG-unresponsive NMIBC with carcinoma in situ (CIS) with or without papillary tumors. In a phase 3 clinical trial including patients with BCG-unresponsive NMIBC with CIS, nadofaragene firadenovec was efficacious in producing complete responses. Nadofaragene firadenovec had an acceptable safety profile and was generally well tolerated, with a small number of patients experiencing a grade 3 treatment-related adverse event and none experiencing a grade 4 or 5 drug-related adverse event. Cystectomy should be considered in patients who do not have a complete response to nadofaragene firadenovec or who have recurrence of CIS. Bacillus Calmette Guerin (BCG) is used in patients with high-risk non-muscle invasive bladder cancer (NMIBC) to reduce recurrence and prevent disease progression; however, a large proportion of patients develop BCG-unresponsive NMIBC. Radical cystectomy to remove the bladder is potentially curative in these patients, but many are unable or unwilling to undergo this major surgery. Nadofaragene firadenovec (Adstiladrin (R)) is a gene therapy administered into the bladder that causes localized expression of interferon (IFN) alpha 2b, which promotes an anti-tumor immune response. It is approved in the USA for the treatment of adults with high-risk BCG-unresponsive NMIBC with carcinoma in situ (CIS) with or without papillary tumors. In a pivotal clinical trial in patients with BCG-unresponsive NMIBC with CIS, nadofaragene firadenovec effectively produced complete responses (i.e. no detectable signs of bladder cancer). Nadofaragene firadenovec had an acceptable safety profile and was generally well tolerated, with most treatment-related adverse events being mild or moderate in severity. Thus, current evidence suggests that nadofaragene firadenovec is an important bladder-sparing treatment option in patients with high-risk BCG-unresponsive NMIBC with CIS.