Background and objective

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.

Methods

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.

Key findings and limitations

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.

Conclusions and clinical implications

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.

中文翻译：

---

转移性肾细胞癌的一线和二线治疗

 背景和目标

近年来，转移性肾细胞癌 （mRCC） 的治疗前景发生了显着变化，从而改善了结果。本综述的目的是为临床医生提供根据当前证据选择一线和二线治疗的实用指南。

 方法

我们严格评估了 mRCC 的全身治疗策略。在 PubMed 和 Embase 中进行了全面的文献检索，同时对截至 2024 年 10 月的指南和会议论文集进行了人工检索。进行了叙述性综述以达成共识，投票用于解决作者之间的不同意见。

主要发现和局限性

一线治疗选择包括基于免疫检查点抑制剂 （ICI） 的组合或酪氨酸激酶抑制剂 （TKI）。4 种联合治疗方案已在国际上获得批准。由于缺乏头对头试验和标准化生物标志物，治疗决策取决于国际转移性 RCC 数据库联盟 （IMDC） 风险评分、功能状态、安全性概况、肉瘤样特征、免疫抑制药物的使用以及立即反应需求等因素。尽管取得了进展，但许多患者在基于 ICI 的治疗中会出现疾病进展，需要进一步治疗。对标准化二线方法的需求仍未得到满足。TKI 单独使用或与依维莫司联合使用，显示出有希望的疗效，而 HIF2a 抑制剂提供了具有良好毒性特征的更新选择。不建议在早期进展后再次使用 ICIs。

结论和临床意义

为了选择最佳的 mRCC 治疗，临床医生必须仔细平衡疗效、毒性和患者偏好，尤其是在一线和二线治疗之间过渡时，以提供个体化护理。