Upper urinary tract urothelial carcinoma (UTUC) is often locally advanced at initial diagnosis and is associated with high recurrence and mortality rates after radical nephroureterectomy (RNU). Adjuvant platinum-based chemotherapy has shown a recurrence-free survival benefit in a randomised phase III trial, while neoadjuvant treatment seems promising in retrospective series. On the contrary, little is known about the role of perioperative immunotherapy and its combination with chemotherapy for UTUC patients, although initial positive results have been published for muscle-invasive bladder cancer.
Against this backdrop, we are running a multi-centre single-arm phase 2 trial of neoadjuvant Durvalumab, a monoclonal antibody targeting programmed cell death ligand 1, combined with Gemcitabine and Cisplatin or Carboplatin for high-risk UTUC patients. The primary outcome is pathological complete response rate at RNU. Secondary endpoints include the partial pathological response rate, safety, as well as disease-free and overall survival. A biomarker analysis is also planned.
Included patients must have a good performance status and harbour a non-metastatic UTUC, considered at high risk of progression, defined as either biopsy-proven high-grade disease or invasive features at imaging with or, more recently, without high-grade cytology at the multidisciplinary team discretion, as specified in the latest amendment. Enrolled patients receive 3 cycles of neoadjuvant immuno-chemotherapy before RNU, and the standard of care thereafter. The trial is registered as NCT04617756 and is supervised by an independent data monitoring committee.
World journal of urology. 2023 Sep 12 [Epub ahead of print]
Giorgio Calleris, Morgan Rouprêt, Thomas Seisen, Lyamin Bendjeddou, Thierry Chevallier, Alexandra Masson-Lecomte, Constance Thibault, Yann Neuzillet, François Audenet, Evanguelos Xylinas, Nadine Houédé
GRC 5 Predictive Onco-Urology Research Group and Urology Department, Pitié-Salpêtrière Hospital, Assistance Publique-Hôpitaux de Paris, Sorbonne University, 75013, Paris, France., GRC 5 Predictive Onco-Urology Research Group and Urology Department, Pitié-Salpêtrière Hospital, Assistance Publique-Hôpitaux de Paris, Sorbonne University, 75013, Paris, France. mroupret@gmail.com., Research and Innovation Department, Nimes University Hospital, 30029, Nimes, France., Department of Biostatistics, Epidemiology, Public Health and Innovation in Methodology (BESPIM), Nimes University Hospital, 30029, Nimes, France., Department of Urology, Saint Louis Hospital, Assistance Publique-Hôpitaux de Paris, Paris Cité University, 75010, Paris, France., Department of Medical Oncology, Assistance Publique-Hôpitaux de Paris, Hopital Européen Georges Pompidou, Paris, France., Department of Urology, Foch Hospital, Paris Saclay University, Suresnes, France., Department of Urology, Hôpital Européen Georges Pompidou, Assistance Publique-Hôpitaux de Paris, Université Paris Cité, Paris, France., Service d'Urologie, Hôpital Bichat-Claude Bernard, Assistance Publique-Hôpitaux de Paris, Université Paris Cité, Paris, France., Gard Cancer Institute, Nimes University Hospital, University of Montpellier, 30029, Nimes, France.