In this review, we discuss which patients with metastatic clear cell renal cell carcinoma (mRCC) may be most suitable for frontline tyrosine kinase inhibitor (TKI) monotherapy, a treatment option supported by emerging long-term efficacy data including overall survival and quality of life. We specifically focus on tivozanib, a potent and selective inhibitor of vascular endothelial growth factor receptor, which has comparable efficacy to other single-agent TKIs in frontline treatment for mRCC while exhibiting fewer off-target side effects.
Combination therapy with TKIs and checkpoint inhibitors (CPIs) and CPI/CPI combination therapies, as well as TKI monotherapy are recommended frontline treatment options for mRCC. Treatment decisions are complex and based on several factors, including the patient's International Metastatic RCC Database Consortium risk status, age, comorbidities, and personal preferences related to response, tolerability, and quality of life. TKIs not only serve as backbone of most combination therapies for mRCC, but also remain a viable monotherapy option in the first-line setting for patients in favorable risk groups and those with contraindications to CPI combination therapies. Given that overall survival benefits have not yet been confirmed for CPI-containing combination regimens in favorable risk patients, we argue that frontline single-agent TKI treatment remains a standard of care option for these patients. This is supported by treatment guidelines, even in the era of TKI/CPI combination therapies.
Current oncology reports. 2024 Nov 20 [Epub ahead of print]
Ricky Frazer, José Ángel Arranz, Sergio Vázquez Estévez, Omi Parikh, Laura-Maria Krabbe, Naveen S Vasudev, Christian Doehn, Norbert Marschner, Tom Waddell, Will Ince, Peter J Goebell
Velindre Cancer Centre, Cardiff, CF14 2TL, UK. ., Hospital General Universitario Gregorio Marañón, Madrid, Spain., Hospital Universitario Lucus Augusti (HULA), Lugo, Spain., Lancashire Teaching Hospitals NHS Foundation Trust, Chorley, UK., Klinik für Urologie, Vivantes Humboldt-Klinikum, Berlin, Germany., Leeds Institute of Medical Research at St James's, Leeds, UK., Urologikum Lübeck, Lübeck, Germany., Clinical Research Institute IOMEDICO, Freiburg, Germany., The Christie NHS Foundation Trust, Manchester, UK., Department of Oncology, Cambridge University NHS Foundation Trust, Cambridge, UK., Uniklinik Erlangen, Urologische und Kinderurologische Klinik, Erlangen, Germany.