转移性透明细胞肾细胞癌中免疫检查点抑制剂治疗的优化药物治疗管理。
摘要
引言：免疫检查点抑制剂（ICI）的问世彻底改变了转移性透明细胞肾细胞癌的管理。尽管取得了这些进展，在没有经过验证的预测性生物标志物的情况下，优化药物治疗选择、序贯治疗和毒性管理仍然具有挑战性。涵盖领域：本综述综合了关键性III期试验（CheckMate 214、KEYNOTE-426、JAVELIN Renal 101、CheckMate 9ER、CLEAR，以及ICI后试验CONTACT-03、TiNivo-2和LITESPARK-011）和真实世界证据，以提供全面的ICI管理框架。…
正文 待译
INTRODUCTION: The introduction of immune checkpoint inhibitors (ICIs) has revolutionized the management of metastatic clear-cell renal cell carcinoma. Despite these gains, optimizing pharmacotherapeutic selection, sequencing, and toxicity management remains challenging without validated predictive biomarkers. AREAS COVERED: This review synthesizes pivotal phase III trials (CheckMate 214, KEYNOTE-426, JAVELIN Renal 101, CheckMate 9ER, CLEAR, and the post-ICI trials CONTACT-03, TiNivo-2 and LITESPARK-011) and real-world evidence to provide a comprehensive ICI management framework. We examine pharmacological principles, risk-stratified first-line selection by International Metastatic RCC Database Consortium (IMDC) criteria, post-ICI sequencing strategies, emerging biomarkers including transcriptomic signatures and kidney injury molecule-1 (KIM-1), immune-related adverse event (irAE) management, treatment duration and tyrosine kinase inhibitor (TKI) dose management, and novel approaches. PubMed/MEDLINE, Embase and the Cochrane Library were searched for articles published between January 2015 and September 2026, supplemented by abstracts from major international oncology congresses and by ClinicalTrials.gov. EXPERT OPINION: Optimal therapy requires integrating IMDC risk, sarcomatoid histology, disease kinetics, and patient preferences into individualized decisions, while extended flat dosing and vigilant irAE management are as critical as regimen selection. HIF-2α inhibition is already entering practice after ICI failure and in the adjuvant setting, and future strategies will move toward dynamic, biology-driven personalization.
English
INTRODUCTION: The introduction of immune checkpoint inhibitors (ICIs) has revolutionized the management of metastatic clear-cell renal cell carcinoma. Despite these gains, optimizing pharmacotherapeutic selection, sequencing, and toxicity management remains challenging without validated predictive biomarkers. AREAS COVERED: This review synthesizes pivotal phase III trials (CheckMate 214, KEYNOTE-426, JAVELIN Renal 101, CheckMate 9ER, CLEAR, and the post-ICI trials CONTACT-03, TiNivo-2 and LITESPARK-011) and real-world evidence to provide a comprehensive ICI management framework.…