Patients with high-risk non-muscle-invasive bladder cancer (NMIBC) often have recurrence or progression after transurethral resection of bladder tumour (TURBT) and subsequent BCG therapy. We aimed to evaluate whether 1 year of durvalumab with BCG could improve outcomes versus BCG alone for these patients.
This randomised, open-label, phase 3 trial enrolled patients aged 18 years or older with BCG-naive, high-risk NMIBC who underwent TURBT. Patients were randomly allocated (1:1:1) to receive intravenous durvalumab (every 4 weeks for 13 cycles) plus intravesical BCG induction (weekly for 6 weeks) and maintenance (three doses at weekly intervals at 3, 6, 12, 18, and 24 months), durvalumab plus BCG induction, or BCG induction and maintenance (comparison group). The primary endpoint was investigator-assessed disease-free survival in the durvalumab plus BCG induction and maintenance group versus the comparison group in the intention-to-treat population. This study is registered at ClinicalTrials.gov (NCT03528694) and EudraCT (2017-002979-26) and is ongoing but is no longer enrolling patients.
Between June 18, 2018, and Oct 2, 2020, 1350 patients were assessed for eligibility, among whom 1018 patients were randomly allocated: 339 to the durvalumab plus BCG induction and maintenance group (of whom 336 [99%] initiated and 180 [53%] completed treatment), 339 to the durvalumab plus BCG induction group (337 [99%] initiated and 239 [71%] completed treatment), and 340 to the comparison group (339 [>99%] initiated and 182 [54%] completed treatment). At a median follow-up of 60·7 months (IQR 51·5-66·5), there were 67 (20%) disease-free survival events in the durvalumab plus BCG induction and maintenance group and 98 (29%) events in the comparison group, resulting in a 32% reduction in the risk of recurrence of high-risk disease or death by any cause with durvalumab plus BCG induction and maintenance versus the comparison group (hazard ratio 0·68 [95% CI 0·50-0·93]; log-rank p=0·015). Among patients who received at least one dose of study treatment, grade 3 or 4 treatment-related adverse events occurred in 71 (21%) of 336 patients in the durvalumab plus BCG induction and maintenance group, 52 (15%) in the durvalumab plus BCG induction only group, and 13 (4%) of 339 patients in the comparison group. No treatment-related adverse events led to death.
Among patients with BCG-naive, high-risk NMIBC, 1 year of durvalumab combined with BCG induction and maintenance therapy showed a statistically significant and clinically meaningful improvement in disease-free survival versus BCG induction and maintenance alone. The combination had a manageable safety profile, consistent with that of the individual therapies. These results support 1 year of durvalumab in combination with BCG induction and maintenance therapy as a potential new treatment for this patient population.
AstraZeneca.
Lancet (London, England). 2025 Oct 17 [Epub ahead of print]
Maria De Santis, Joan Palou Redorta, Hiroyuki Nishiyama, Michał Krawczyński, Artur Seyitkuliev, Andrey Novikov, Félix Guerrero-Ramos, Ruslan Zukov, Minoru Kato, Takashi Kawahara, Lieven Goeman, Javier Puente, Eva Hellmis, Thomas Powles, Piotr Radziszewski, Kilian M Gust, Paul Vasey, Pierre Bigot, Yves Fradet, Jarmo Hunting, Jon Armstrong, Suliman Boulos, Stephan Hois, Neal D Shore, POTOMAC Investigators
Department of Urology, Charité Universitätsmedizin Berlin, Berlin, Germany; Department of Urology, Medical University of Vienna, Vienna, Austria., Department of Urology, Fundació Puigvert, Universitat Autònoma de Barcelona, Barcelona, Spain., Department of Urology, University of Tsukuba, Ibaraki, Japan., Clinical Research Center, Poznań, Poland., Saint Petersburg Hospital of the Russian Academy of Sciences, Saint Petersburg, Russia., North-Western State Medical University, Saint Petersburg, Russia., Department of Urology, Hospital Universitario 12 de Octubre, Madrid, Spain., Krasnoyarsk State Medical University, Krasnoyarsk Regional Clinical Cancer Center, Krasnoyarsk, Russia., Department of Urology, Osaka Metropolitan University, Osaka, Japan., Departments of Urology and Renal Transplantation, Yokohama City University Medical Center, Yokohama, Japan., Department of Development and Regeneration, University Hospitals Leuven, Leuven, Belgium., Medical Oncology Department, Hospital Clínico San Carlos, Madrid, Spain., Urologicum-Duisburg, Duisburg, Germany., Barts Cancer Institute Biomedical Research Centre, Queen Mary University of London, Barts Health NHS Trust, London, UK., Department of General, Oncological and Functional Urology, Medical University of Warsaw, Warsaw, Poland., Department of Urology and Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria., Icon Cancer Centre Wesley, Auchenflower, QLD, Australia., Department of Urology, Angers University Hospital, Angers, France., Centre de Recherche du CHU de Québec, Oncology Division, CHU de Québec, Université Laval, Québec City, QC, Canada., Department of Medical Oncology, St Antonius Hospital, Utrecht, Netherlands., Oncology Biometrics, AstraZeneca, Cambridge, UK., Late-stage Development Oncology R&D, AstraZeneca, Cambridge, UK., Late-stage Development Oncology R&D, AstraZeneca, Gaithersburg, MD, USA., START Carolinas/Carolina Urologic Research Center, Myrtle Beach, SC, USA. Electronic address: .
PubMed http://www.ncbi.nlm.nih.gov/pubmed/41115436