Frazer Ricky, Arranz José Ángel, Estévez Sergio Vázquez, Parikh Omi, Krabbe Laura-Maria, Vasudev Naveen S, Doehn Christian, Marschner Norbert, Waddell Tom, Ince Will, Goebell Peter J
Velindre Cancer Centre, Cardiff, CF14 2TL, UK.
Hospital General Universitario Gregorio Marañón, Madrid, Spain.
Curr Oncol Rep. 2024 Dec;26(12):1639-1650. doi: 10.1007/s11912-024-01613-7. Epub 2024 Nov 20.
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.
在本综述中，我们讨论哪些转移性透明细胞肾细胞癌（mRCC）患者可能最适合一线酪氨酸激酶抑制剂（TKI）单药治疗，这一治疗选择得到了包括总生存期和生活质量在内的新的长期疗效数据的支持。我们特别关注替沃扎尼，一种强效且选择性的血管内皮生长因子受体抑制剂，它在mRCC的一线治疗中与其他单药TKI具有相当的疗效，同时表现出较少的脱靶副作用。
TKI与检查点抑制剂（CPI）联合治疗、CPI/CPI联合治疗以及TKI单药治疗都是推荐的mRCC一线治疗选择。治疗决策复杂，基于多个因素，包括患者的国际转移性肾细胞癌数据库联盟风险状态、年龄、合并症以及与反应、耐受性和生活质量相关的个人偏好。TKI不仅是大多数mRCC联合治疗的基础，而且对于低风险组患者以及有CPI联合治疗禁忌证的患者，在一线治疗中仍是一种可行的单药治疗选择。鉴于在低风险患者中含CPI的联合治疗方案尚未证实有总生存期获益，我们认为一线单药TKI治疗仍是这些患者的标准治疗选择。这得到了治疗指南的支持，即使在TKI/CPI联合治疗时代也是如此。
