The treatment landscape for metastatic renal cell carcinoma (mRCC) has evolved significantly in recent years, leading to improved outcomes. The aim of this review is to provide clinicians with a practical guide for selecting first- and second-line treatments on the basis of current evidence.
We critically evaluated systemic treatment strategies for mRCC. A comprehensive literature search was conducted in PubMed and Embase, alongside manual searches of guidelines and conference proceedings up to October 2024. A narrative review was performed to reach a consensus, with voting used to resolve differing opinions among authors.
First-line treatment options include immune checkpoint inhibitor (ICI)-based combinations or tyrosine kinase inhibitors (TKIs). Four combination regimens have been approved internationally. Owing to the lack of head-to-head trials and standardized biomarkers, treatment decisions rely on factors such as International Metastatic RCC Database Consortium (IMDC) risk score, functional status, safety profiles, sarcomatoid features, use of immunosuppressive drugs, and need for immediate response. Despite advances, many patients will experience disease progression on ICI-based therapy, necessitating further treatment. The need for standardized second-line approaches remains unmet. TKIs, alone or with everolimus, show promising efficacy, while HIF2a inhibitors offer newer options with a favorable toxicity profile. Rechallenge with ICIs after early progression is not recommended.
For optimal mRCC treatment selection, clinicians must carefully balance efficacy, toxicity, and patient preferences, especially when transitioning between first- and second-line therapies, to provide individualized care.
European urology. 2024 Nov 05 [Epub ahead of print]
Regina Barragan-Carrillo, Eddy Saad, Renee-Maria Saliby, Maxine Sun, Laurence Albiges, Axel Bex, Daniel Heng, Arnaud Mejean, Robert J Motzer, Elizabeth R Plimack, Thomas Powles, Brian I Rini, Tian Zhang, Toni K Choueiri
Department of Medical Oncology, City of Hope Comprehensive Cancer Center, Duarte, CA, USA., Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA., Institut Gustave Roussy, Paris, France., Specialist Centre for Kidney Cancer, Royal Free NHS Foundation Trust, University College London Division of Surgery and Interventional Science, London, UK., Department of Oncology, Tom Baker Cancer Centre, Calgary, Canada., Department of Urology, Hôpital Européen Georges Pompidou, Paris, France., Genitourinary Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Department of Hematology/Oncology, Fox Chase Cancer Center, Philadelphia, PA, USA., Barts Health NHS Trust and the Royal Free NHS Foundation Trust, Barts Cancer Institute, London, UK; Queen Mary University of London, London, UK., Vanderbilt-Ingram Cancer Center, Nashville, TN, USA., Division of Hematology and Oncology, Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX, USA., Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA. Electronic address: .