BACKGROUND: Pembrolizumab has demonstrated efficacy in improving disease-free survival (DFS) and overall survival (OS) as adjuvant therapy in clear cell renal cell carcinoma (ccRCC) at a higher risk of recurrence. However, real-world data on its effectiveness and safety remain limited. This study evaluates DFS, OS and severe adverse events (SAEs) associated with adjuvant pembrolizumab in a multicenter international cohort. METHODS: This retrospective analysis included 311 ccRCC patients treated with adjuvant pembrolizumab across 40 hospitals in 12 countries from the ARON-1 dataset. Eligible patients had histologically confirmed ccRCC with high relapse risk and received up to 17 cycles of pembrolizumab. The primary objective was DFS, with OS and safety as secondary objectives. Kaplan-Meier survival estimates, Cox proportional hazards models and log-rank tests were used for statistical analysis. RESULTS: At a median follow-up of 15.4-month, 2-year OS and DFS rates were 95% and 69%, respectively. Recurrence occurred in 20% of patients, primarily in the lungs (11%) and bones (5%). DFS was significantly impaired in patients < 65 years (HR 2.14, p = 0.005), N1 disease (HR 5.42, p = 0.004) and sarcomatoid dedifferentiation (HR 2.54, p = 0.007). SAEs led to 19% treatment discontinuation, with colitis (4%), hypertransaminasemia (4%) and nephritis (3%) as the most common events. The study's retrospective nature and short follow-up limit long-term outcome assessments. CONCLUSIONS: This large real-world study confirms pembrolizumab's effectiveness and manageable safety profile in the adjuvant setting for intermediate-high and high-risk ccRCC. Further research is needed to refine patient selection strategies and evaluate long-term outcomes.

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

Clinical Oncology Sociedad de Oncología y Hematología del Cesar Valledupar Colombia

Department of Clinical Oncology and Radiotherapy University Hospital Hradec Kralove Hradec Kralove Czechia

Department of Health Sciences Section of Clinical Pharmacology and Oncology University of Florence Florence Italy

Department of Hematology and Oncology Emory University School of Medicine Atlanta GA USA

Department of Medical and Surgical Sciences University of Bologna Bologna Italy

Department of Medical Oncology Faculty of Medicine Ankara University Türkiye; Westwood Ankara KS 06620 USA

Department of Medical Oncology Hospital Ramón y Cajal Madrid Spain

Department of Medical Oncology MD Anderson Cancer Center Madrid Madrid Spain

Department of Medicine and Surgery University of Parma Parma Italy

Department of Oncology 2nd Faculty of Medicine Charles University and University Hospital Motol 5 Uvalu 84 150 06 Prague Czech Republic

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

Department of Oncology Radiotherapy Alexandru Trestioreanu Institute of Oncology ''Carol Davila'' University of Medicine and Pharmacy 020021 Bucharest Romania

Department of Uro Oncology Maria Sklodowska Curie National Research Institute of Oncology Warsaw Warsaw Poland

Department of Urology Medical University of Innsbruck Innsbruck Austria

Department of Urology University Hospital Bonn Bonn Germany

Division of Medical Oncology Department of Internal Medicine Markey Cancer Center University of Kentucky Lexington KY USA

Division of Medical Oncology Department of Internal Medicine University of Kansas Cancer Center Kansas city USA

Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán Mexico City Mexico

Interdisciplinary Department of Medicine University of Bari ''Aldo Moro'' Bari Italy

Latin American Cooperative Oncology Group LACOG Porto Alegre Brazil

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

Oncology 1 Unit Department of Oncology Istituto Oncologico Veneto IOV IRCCS Padua Italy

Oncology and Hematology Department Hospital Sírio Libanês Brasília Brazil

Oncology Unit 2 University Hospital of Pisa 56126 Pisa Italy

Oncology Unit Hospital Israelita Albert Einstein São Paulo SP Brazil

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

Servicio de Oncología Hospital Universitario La Paz Madrid Spain

Unit of Medical Oncology and Biomolecular Therapy and C R E A T E Center for Research and Innovation Medicine Department of Medical and Surgical Sciences University of Foggia Policlinico Riuniti Foggia Italy

Winship Cancer Institute of Emory University Atlanta GA USA

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