Safety and efficacy of neoadjuvant immunotherapy with durvalumab (MEDI 4736) in combination with neoadjuvant chemotherapy (gemcitabine/cisplatin or carboplatin) in patients with operable high-risk upper tract urothelial carcinoma.
Year: 2025
Type: conference-abstract
Abstract: 661 Background: Most patients following radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC) face a poor prognosis. Combination of chemotherapy and immunotherapy in neoadjuvant setting have demonstrated survival improvement in several tumors. Additional systemic therapy in a neoadjuvant setting may prolong survival for UTUC patients, especially those after RNU who are ineligible to receive nephrotoxic chemotherapy. Methods: Phase 2 clinical trial (NCT04617756) was conducted in 10 French centers. Eligible patients had non metastatic, high-grade disease on ureteroscopic tumor biopsy or on urine cytology and infiltrative aspect of renal pelvis/ureteral wall on CT imaging. Subjects received a combination of: Durvalumab/Gemcitabine/Cisplatin (cohort 1) or Carboplatin (cohort 2) every 3 weeks for a total of 4 cycles based on glomerular filtration rate, prior to RNU. The primary objective was to assess the pathological complete response (ypT0) rate (pCR) of each combination. Results: A total of 50 patients were enrolledbetween 2021 and 2023 (31 in cohort 1 and 19 in cohort 2). Median age was 66 years old (range 38-79), 58% were males. 90% of patients (44) received 4 cycles of treatment, 3 patients 3 cycles and 2 patients received 2 cycles. Five patients switched for carboplatin during chemotherapy. We observed in cohort 1 : 20/31 (65%) patients with non infiltrative residual tumor; In cohort 2 : 9/19 (42%) patients (table). Secondary endpoint was safety, no immunotherapy-mediated AE was observed, 2 patients had Grade 3 neutropenia, 1 grade 4, 1 patient had grade 3 thrombopenia and 1 grade 3 anemia. Conclusions: Combination of durvalumab with platin-based chemotherapy, especially cisplatin, showed promising activity in UTUC, with the occurrence of complete responses and a high rate of non-infiltrative residual tumor. Safety profile was secure without increasing surgical risk. A randomized Phase 3 controlled study comparing neoadjuvant chemotherapy with chemotherapy combined with immunotherapy in patients with high-risk localized UTUC (iNDUCT-3) will open soon to validate these encouraging results. Clinical trial information: NCT04617756 . Pathological response rate. ypT0 ypTIS /ypTa ypT1 ypT2 ypT3 ypT4 Missing data Withdrawal surgery Total Cis-Gem Durva 4 (13%) 5 (16%) 11 (36%) 1 (3%) 6 (19%) 1 (3%) 1 2 31 Carbo-Gem Durva 1 (5%) 6 (32%) 1 (5%) 3 (16%) 5 (26%) 1 (5%) 1 1 19
Source: Journal of Clinical Oncology
Authors: Nadine Houede, Thierry Chevallier, Jaffrelot Loic, Constance Thibault, Neuzillet Yann, Christine Abraham Jaillon, Alexandra Masson-Lecomte, Gwenaelle Gravis, Sophie Tartas, Damien Pouessel, Brigitte Laguerre, Francois Audenet, Evanguelos Xylinas, Luquiens Guillaume, Morgan Roupret
Institutions: Université de Montpellier, Centre Hospitalier Universitaire de Nîmes, Pitié-Salpêtrière Hospital, Université Paris Cité, Assistance Publique – Hôpitaux de Paris, Hôpital Européen Georges-Pompidou, Université de Versailles Saint-Quentin-en-Yvelines, Université Paris-Saclay, Hôpital Foch, Inserm, Commissariat à l'Énergie Atomique et aux Énergies Alternatives, Hôpital Saint-Louis, HIPI - Immunologie humaine, physiopathologie et immunithérapie, Centre National de la Recherche Scientifique, Aix-Marseille Université, Centre de Recherche en Cancérologie de Marseille, Institut Paoli-Calmettes, Institut universitaire du cancer de Toulouse Oncopole, Centre Eugène Marquis, Hôpital Bichat-Claude-Bernard, Université de Nîmes, Sorbonne Université, Onco-Urologie Prédictive
Language: English
Subfield: Surgery
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W4407701588