Our systematic review focuses on the role of gene therapies in patients with BCG-unresponsive NMIBC. The available data are encouraging in terms of both efficacy and tolerability. In the phase III CS-007 study, nadofaragene firadenovec, an adenoviral vector encoding INFa2b and the first gene therapy approved in the United States for BCG-unresponsive NMIBC with carcinoma in situ (CIS), achieved a complete response rate of 54% at 3 months, with bladder preservation in approximately 43% of patients at 5 years. Furthermore, in the BOND-003 study, cretostimogene grenadenorepvec demonstrated a complete response rate of 51% at one year. Finally, the non-viral gene therapy detalimogene voraplasmid, evaluated in the LEGEND study, achieved a complete response rate of 47% at six months. Overall, the safety profile appears favorable, with the incidence of grade ≥3 adverse events remaining below 4%.
Currently, one of the major challenges lies in the personalization of care, particularly through the identification of urinary biomarkers to determine which patients are most likely to respond to one treatment rather than another, given the high cost of these innovative therapies.
Numerous bladder-preservation options are currently available; however, no study has compared these strategies with one another, as radical cystectomy remains the standard of care. Recently, as an example, the immunotherapy Anktiva in combination with BCG has received marketing authorization from the European Medicines Agency (EMA) for patients with BCG-unresponsive non–muscle-invasive bladder cancer with CIS.
Written by: Constance Bertrand,1 Idir Ouzaid,1 Felix Guerrero-Ramos,1-4 Gautier Marcq,5,6 John P Sfakianos,7 Evanguelos Xylinas,1 Pierre-Etienne Gabriel1
- Department of Urology, Bichat Claude-Bernard Hospital, Assistance Publique-Hôpitaux de Paris Nord, University Paris Cité, Paris, France.
- Hospital Universitario 12 de Octubre, Madrid, Spain.
- ROC Clinic, Madrid, Spain.
- Department of Urology, Hospital Universitario HM Sanchinarro, Madrid, Spain.
- Urology Department, Claude Huriez Hospital, CHU Lille, Lille, France.
- Univ. Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, UMR9020-U1277, CANTHER, Cancer Heterogeneity Plasticity and Resistance to Therapies, Lille, France.
- Department of Urology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.