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Perioperative Durvalumab with Neoadjuvant Chemotherapy in Operable Bladder Cancer.

Thomas Powles1, James W F Catto1, Matthew D Galsky1

  • 1From Barts Cancer Institute, Queen Mary University of London, Barts Health NHS Trust Biomedical Research Centre, London (T.P.), the Division of Clinical Medicine, School of Medicine and Population Health, University of Sheffield, and Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield (J.W.F.C.), and AstraZeneca, Cambridge (J.A.) - all in the United Kingdom; the Division of Hematology and Medical Oncology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai (M.D.G.), the Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center (H.A.-A.), and AstraZeneca (A.G.) - all in New York; the Departments of Urology and Biochemistry, Northwestern University Feinberg School of Medicine, Chicago (J.J.M.); the University of Tsukuba, Tsukuba, Japan (H.N.); Internal Medical 3, Vietnam National Cancer Hospital, Hanoi (T.Q.V.); the Department of Experimental and Clinical Medicine, University of Florence, and the Medical Oncology Unit, Careggi University Hospital - both in Florence, Italy (L.A.); Maria Skłodowska-Curie National Research Institute of Oncology, Warsaw, Poland (P.W.); the Volga District Medical Center, Federal Medical-Biological Agency, Nizhny Novgorod, Russia (V.A.); Hospital Alemão Oswaldo Cruz, Sao Paulo (A.G.K.); the Department of Urology, Kyungpook National University Chilgok Hospital, Daegu, South Korea (T-H.K.); Medical Oncology, Vall d´Hebron Institute of Oncology, Hospital Universitari Vall d´Hebron, Vall d´Hebron Barcelona Hospital Campus, Barcelona (C.S.); the Department of Urology, China Medical University Hospital and School of Medicine, College of Chinese Medicine, China Medical University, Taichung, Taiwan (C-H.C.); the Department of Urology, Marien Hospital Herne, Ruhr University Bochum, Herne, Germany (F.R.); Istanbul University-Cerrahpaşa, Cerrahpaşa School of Medicine, Istanbul, Turkey (M.Ö.); BC Cancer-Vancouver, Vancouver, BC, Canada (B.J.E.); Mater Hospital Brisbane, Mater Misericordiae, and the School of Clinical Medicine, Mater Clinical Unit, University of Queensland - both in Brisbane, Australia (N.O.); the Department of Oncology, First Faculty of Medicine, Charles University and Thomayer Hospital, Prague, Czech Republic (T.B.); the Institute of Oncology, Sheba Medical Center, Ramat Gan, and the Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv - both in Israel (M.G.); the University of Iowa Hospitals and Clinics, Holden Comprehensive Cancer Center, Iowa City (Y.Z.); AstraZeneca, Gaithersburg, MD (S.H.); and the Department of Medical Oncology, Netherlands Cancer Institute, Amsterdam (M.S.H.).

The New England Journal of Medicine
|September 16, 2024
PubMed
Summary
This summary is machine-generated.

Adding perioperative durvalumab to neoadjuvant chemotherapy significantly improved event-free and overall survival for muscle-invasive bladder cancer patients undergoing radical cystectomy. This combination therapy offers a promising advancement in bladder cancer treatment.

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Area of Science:

  • Oncology
  • Urothelial Carcinomas
  • Clinical Trials

Background:

  • Standard treatment for muscle-invasive bladder cancer (MIBC) involves neoadjuvant chemotherapy followed by radical cystectomy for cisplatin-eligible patients.
  • Perioperative immunotherapy is being investigated as a strategy to enhance treatment outcomes in MIBC.

Purpose of the Study:

  • To evaluate the efficacy and safety of adding perioperative durvalumab to neoadjuvant chemotherapy and radical cystectomy in cisplatin-eligible MIBC patients.
  • To compare event-free survival (EFS) and overall survival (OS) between patients receiving durvalumab plus chemotherapy and those receiving chemotherapy alone.

Main Methods:

  • A phase 3, open-label, randomized trial (NIAGARA) assigned 1063 cisplatin-eligible MIBC patients to receive neoadjuvant durvalumab plus gemcitabine-cisplatin or gemcitabine-cisplatin alone.
  • Patients then underwent radical cystectomy, followed by adjuvant durvalumab in the experimental arm.
  • Event-free survival was a primary endpoint, and overall survival was a key secondary endpoint.

Main Results:

  • Event-free survival at 24 months was significantly higher in the durvalumab group (67.8%) compared to the control group (59.8%) (HR, 0.68; P<0.001).
  • Overall survival at 24 months was also significantly improved with durvalumab (82.2%) versus the control (75.2%) (HR, 0.75; P=0.01).
  • Rates of grade 3-4 treatment-related adverse events were similar between groups (40.6% vs 40.9%), with rare treatment-related deaths (0.6% in each group).

Conclusions:

  • Perioperative durvalumab combined with neoadjuvant chemotherapy demonstrated significant improvements in both event-free and overall survival for MIBC patients.
  • This regimen represents a potential new standard of care, offering enhanced survival benefits with manageable toxicity.
  • The study provides robust evidence for the benefit of adding immunotherapy to the established neoadjuvant chemotherapy and cystectomy pathway for MIBC.