BACKGROUND: The benefit of immune checkpoint inhibitors (ICIs) for poor performance status patients with advanced urothelial carcinoma (UC) remains unknown. OBJECTIVE: In the present sub-analysis of the ARON-2 study, we investigated the role of pembrolizumab for advanced UC patients with ECOG (Eastern Cooperative Oncology Group) performance status (ECOG-PS) 2. PATIENTS AND METHODS: Patients aged ≥ 18 years with a cytologically and/or histologically confirmed diagnosis of advanced UC progressing or recurring after platinum-based therapy and treated with pembrolizumab between 1 January 2016 to 1 April 2024 were included. In this sub-analysis we focused on patients with ECOG-PS 2. RESULTS: We included 1,040 patients from the ARON-2 dataset; of these, 167 patients (16%) presented an ECOG-PS 2. The median overall survival (OS) was 14.8 months (95% confidence interval (CI) 12.5-16.1) in the overall study population, 18.2 months (95% CI 15.8-22.2) in patients with ECOG-PS 0-1, and 3.7 months (95% CI 3.2-5.2) in subjects with ECOG-PS 2 (p < 0.001). The median progression-free survival (PFS) in the overall study population was 5.3 months (95% CI 4.3-97.1), 6.2 months (95% CI 5.5-97.1) in patients with ECOG-PS 0-1, and 2.8 months (95% CI 2.1-3.4) in patients with ECOG-PS 2. Among the latter, liver metastases and progressive disease during first-line therapy were significant predictors of OS at both univariate and multivariate analyses. For PFS, univariate and multivariate analyses showed a prognostic role for lung metastases, liver metastases, and progressive disease during first-line therapy. CONCLUSIONS: This large real-world evidence study suggests the effectiveness of second-line pembrolizumab for mUC patients with poor performance status. The presence of liver metastases and progressive disease during first-line therapy is associated with worse clinical outcomes and, thus, should be taken into account when making treatment decisions in clinical practice.

Clinical Oncology Sociedad de Oncología y Hematología del Cesar Valledupar Colombia

Department of Health Sciences Section of Clinical Pharmacology and Oncology University of Florence Viale Pieraccini 6 50139 Florence Italy

Department of Hemato Oncology Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran Mexico City Mexico

Department of Medical and Surgical Sciences University of Bologna Bologna Italy

Department of Medical Oncology Bakirköy Dr SadiKonuk Training and Research Hospital Istanbul Türkiye

Department of Medical Oncology Faculty of Medicine Ankara University 06620 Ankara Turkey

Department of Medical Oncology Hospital Ramón y Cajal Madrid Spain

Department of Medicine and Surgery Federico 2 University Naples Italy

Department of Medicine and Surgery University of Parma Parma Italy

Department of Oncology and Hematology Oncology Unit Santa Maria delle Croci Hospital AUSL Romagna Ravenna Italy

Department of Urology Medical University of Innsbruck Innsbruck Austria

Department of Urology Saitama Medical Center Saitama Medical University Saitama Japan

Division of Medical Oncology National Cancer Centre Singapore Singapore Singapore

Escuela de Medicina Universidad Panamericana Mexico City Mexico

Faculty of Medicine Masaryk University Brno Czech Republic

Hospital Israelita Albert Einstein São Paulo SP Brazil

Hospital Sírio Libanês Brasília DF Brazil

Latin American Cooperative Oncology Group LACOG Porto Alegre Brazil

Masaryk Memorial Cancer Institute Brno Czech Republic

Medical Oncology 1 IRCCS Regina Elena National Cancer Institute Rome Italy

Medical Oncology Department Fondazione IRCCS Istituto Nazionale dei Tumori Via Giacomo Venezian 1 Milan Italy

Medical Oncology IRCCS Azienda Ospedaliero Universitaria di Bologna Bologna Italy

Medical Oncology Unit Azienda Ospedaliera Universitaria Consorziale Policlinico di Bari Bari Italy

Medical Oncology Unit Macerata Hospital Macerata Italy

Medical Oncology Unit University Hospital of Parma Parma Italy

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

Oncology Unit A R N A S Civico Palermo Italy

S S D C O r O Bed Management Presa in Carico TDM IRCCS Istituto Tumori Giovanni Paolo 2 Viale Orazio Flacco 65 70124 Bari Italy

Samsung Medical Center Sungkyunkwan University School of Medicine Seoul Korea

Unità di Oncologia Medica Azienda Ospedaliero Universitaria di Cagliari Cagliari Italy

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