Georgetown Lombardi Comprehensive Cancer Center, Washington, DC, USA.
The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Cancer Treat Rev. 2018 Nov;70:127-137. doi: 10.1016/j.ctrv.2018.07.009. Epub 2018 Jul 20.
There has been significant progress in the treatment of patients with advanced clear cell renal cell carcinoma (ccRCC), with improved knowledge of disease biology and the introduction of targeted agents and immunotherapies. In this review, we discuss current and emerging first-line treatment options, including recent approvals of the tyrosine kinase inhibitor (TKI) cabozantinib and the immunotherapy combination of nivolumab (anti-programmed cell death 1 [PD-1])/ipilimumab (anti-cytotoxic T-lymphocyte-associated antigen 4 [CTLA-4]), and initial outcomes with the combination of atezolizumab (anti-PD-ligand 1 [PD-L1])/bevacizumab (anti-vascular endothelial growth factor [VEGF]). Key clinical data are reviewed, as these novel first-line treatments offer significant improvement, particularly for patients classified as intermediate/poor risk for whom previously available therapies have demonstrated limited efficacy. Treatment recommendations based on clinical evidence and expert opinion are discussed. We also review ongoing studies investigating combinations of checkpoint inhibitors with TKIs, including cabozantinib and axitinib, and with other novel immunomodulatory agents, and the potential role of single-agent immunotherapy for select patients. With a growing treatment armamentarium, identification and validation of biomarkers will be crucial for optimizing first-line selection and treatment sequences.
在治疗晚期透明细胞肾细胞癌（ccRCC）患者方面已经取得了重大进展，对疾病生物学的认识不断提高，并且引入了靶向药物和免疫疗法。在这篇综述中，我们讨论了当前和新兴的一线治疗选择，包括酪氨酸激酶抑制剂（TKI）卡博替尼和免疫治疗联合纳武单抗（抗程序性细胞死亡 1 [PD-1]）/伊匹单抗（抗细胞毒性 T 淋巴细胞相关抗原 4 [CTLA-4]）的最新批准，以及阿替利珠单抗（抗 PD-配体 1 [PD-L1]）/贝伐珠单抗（抗血管内皮生长因子 [VEGF]）联合治疗的初步结果。我们回顾了关键的临床数据，因为这些新的一线治疗方法提供了显著的改善，特别是对于以前的治疗方法疗效有限的中/高危风险患者。根据临床证据和专家意见讨论了治疗建议。我们还回顾了正在进行的研究，这些研究调查了检查点抑制剂与 TKI（包括卡博替尼和阿昔替尼）的联合应用，以及与其他新型免疫调节药物的联合应用，以及单药免疫疗法在某些患者中的潜在作用。随着治疗方法的不断增加，识别和验证生物标志物对于优化一线选择和治疗顺序至关重要。
