For patients with high-risk non-muscle-invasive bladder cancer (NMIBC) for whom bacillus Calmette-Guérin (BCG) treatment has failed, bladder preservation is a high priority. Immune checkpoint inhibitors have shown promise, but systemic administration is associated with substantial toxicity. In this single-arm phase 2 study, 30 patients with NMIBC after BCG failure were treated with intravesical durvalumab every 6 wk. The maximum tolerated dose in the run-in phase was 1000 mg. In phase 2, the high-grade relapse (HGR)-free rate at 1 yr after completing therapy was 39% (95% confidence interval [CI] 18-59%). HGR-free rates at 1, 3, and 6 mo after completing study treatment were 70% (95% CI 45-85%), 55% (95% CI 31-74%), and 39% (95% CI 18-59%), respectively. At 13 mo after completing enrolment, four patients in phase 2 had experienced progression to stage ≥T2; the 1-yr bladder-intact survival rate was 78% (95% CI 57-89%). The only treatment-related adverse event was grade 1 haematuria in five patients (17%). In conclusion, intravesical durvalumab 1000 mg every 6 wk is feasible after BCG failure in patients with high-risk NMIBC, with negligible toxicity and encouraging efficacy. Intravesical durvalumab may be more attractive than systemic administration of immune checkpoint inhibitors and warrants further investigation as a treatment for NMIBC. This trial is registered on ClinicalTrials.gov as NCT03759496.
European urology. 2025 Jan 17 [Epub ahead of print]
Charalampos Fragkoulis, Aristotelis Bamias, Nikos Gavalas, Kimon Tzannis, Evangelos Fragiadis, Alexandros Pinitas, Panayiotis V Stamatakos, George Papadopoulos, George Stathouros, Xanthippi Grammatoglou, Penelope Korkolopoulou, Christina Zoubouli, Konstantinos Stravodimos, Konstantinos Ntoumas, Dionysios Mitropoulos, Andreas Skolarikos, Athanasios Papatsoris
Urology Department, Georgios Gennimatas Hospital, Athens, Greece., 2nd Propaedeutic Department of Internal Medicine, Attikon University Hospital, National & Kapodistrian University of Athens, Athens, Greece. Electronic address: ., 2nd Propaedeutic Department of Internal Medicine, Attikon University Hospital, National & Kapodistrian University of Athens, Athens, Greece., Hellenic Genito-Urinary Cancer Group, Athens, Greece., 1st Urology Department, Laikon Hospital, National & Kapodistrian University of Athens, Athens, Greece., 2nd Urology Department, Sismanoglion Hospital, National & Kapodistrian University of Athens, Athens, Greece., Histopathology Department, Georgios Gennimatas Hospital, Athens, Greece., 1st Histopathology Department, Laikon Hospital, National & Kapodistrian University of Athens, Athens, Greece., Histopathology Department, Sismanoglion Hospital, Athens, Greece.