Upper tract urothelial carcinoma (UTUC) accounts for the 5-10% of all urothelial carcinomas (UCs). In this analysis, we reported the real-world data from the ARON-2 study (NCT05290038) on the efficacy of pembrolizumab in patients with UTUC who recurred or progressed after platinum-based chemotherapy. Medical records of patients with metastatic UTUC treated with pembrolizumab as second-line therapy were reviewed from 34 institutions in 14 countries. Patients were assessed for overall survival (OS), progression-free survival (PFS), and overall response rate (ORR). Univariate and multivariate analyses were used to explore the association of variables of interest with OS and PFS. 235 patients were included in our analysis. Median OS was 8.6 months (95% CI 6.6-12.1), the 1 year OS rate was 43% while the 2 years OS rate 29%. The median PFS was 5.1 months (95% CI 3.9-6.9); 46% of patients were alive at 6 months, 34% at 12 months and 25% at 24 months. According to RECIST 1.1, 18 patients (8%) experienced complete response (CR), 57 (24%) partial response (PR), 44 (19%) stable disease (SD), and 116 (49%) progressive disease (PD), with an ORR of 32%. Our study confirms the effectiveness of pembrolizumab in patients pretreated with a platinum-based combination, irrespective of their sensitivity to the first-line treatment and of their histology. In addition, we emphasized the limited benefit of the treatment with pembrolizumab in patients with hepatic metastases and poor ECOG performance status.

1 R C C S Istituto Tumori Giovanni Paolo 2 Viale Orazio Flacco 65 70124 Bari Italy

Biomedical Center Faculty of Medicine in Pilsen Charles University Pilsen Czech Republic

Centro Paulista de Oncologia Grupo Oncoclínicas Hospital Albert Einstein São Paulo SP Brazil

Clinical Oncology Sociedad de Oncología y Hematología del Cesar Valledupar Colombia

Department of Medical and Surgical Sciences University of Bologna Bologna Italy

Department of Medical Oncology Bakirköy Dr SadiKonuk Training and Research Hospital Tevfik Saglam St No 11 BakirkoyZuhuratbaba District Istanbul Turkey

Department of Medical Oncology Hospital Ramón y Cajal Madrid Spain

Department of Medical Oncology IRCCS San Raffaele Hospital Milan Italy

Department of Medical Oncology King Hussein Cancer Center Amman Jordan

Department of Medical Oncology Maggiore della Carità University Hospital Novara Italy

Department of Oncology and Radiotherapeutics Faculty of Medicine and University Hospital in Pilsen Charles University Pilsen Czech Republic

Department of Urology Medical University of Innsbruck Anichstrasse 35 6020 Innsbruck Austria

Department of Urology Saitama Medical Center Saitama Medical University Saitama Japan

Latin American Cooperative Oncology Group LACOG Porto Alegre Brazil

Latin American Cooperative Oncology Group LACOG Porto Alegre RS Brazil

Markey Cancer Center University of Kentucky Lexington KY USA

Medical Oncology 1 IRCCS Regina Elena National Cancer Institute Rome Italy

Medical Oncology IRCCS Azienda Ospedaliero Universitaria di Bologna Bologna Italy

Medical Oncology Unit Department of Medicine and Surgery University Hospital of Parma University of Parma Parma Italy

Medical Oncology Unit Medicine and Pharmacy Faculty National Institute of Oncology Mohamed 5 University Rabat Morocco

Oncology and Hematology Department Hospital Santa Lucia SHLS 716 Cj C Brasília DF 70390 700 Brazil

Oncology Unit 2 University Hospital of Pisa 56126 Pisa Italy

Oncology Unit Macerata Hospital Macerata Italy

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