Division of Urologic Oncology.
Divsion of Medical Oncology, The Ohio State University Comprehensive Cancer Center, Columbus, Ohio.
Curr Opin Oncol. 2023 May 1;35(3):206-217. doi: 10.1097/CCO.0000000000000939.
The purpose of this review is to highlight the most recent changes in the management of advanced renal cell carcinoma, a complicated and ever-changing field of research.
A recent meta-analysis examining combination therapy favors nivolumab plus cabozantinib as the overall survival leader in doublet therapy. Initial results on the first ever trial of triplet therapy have demonstrated improved progression-free survival over current standard of care. The hypoxia-inducible factor-2α (HIF-2α) inhibitor belzutifan is FDA approved for patients with von Hippel-Lindau disease and is currently being investigated in patients with nonhereditary renal cell carcinoma. The new glutamate synthesis inhibitor, telaglenastat, perhaps confers synergistic benefit when combined with everolimus, but combination with cabozantinib was not so effective. Dual mammalian target of rapamycin (mTOR) inhibition with sapanisertib does not appear to be an effective therapeutic option. New biomarkers and targets are actively being investigated. Four recent trials examining alternative agents to pembrolizumab in the adjuvant setting did not demonstrate an improvement in recurrence-free survival. Cytoreductive nephrectomy in the combination therapy era is supported by retrospective data; clinical trials are recruiting patients.
The last year ushered in novel approaches of varying success for managing advanced renal cell carcinoma, including triplet therapy, HIF-2α inhibitors, metabolic pathway inhibitors, and dual mTOR inhibitors. Pembrolizumab remains the only modern therapy available in the adjuvant setting, and the waters surrounding cytoreductive nephrectomy are still murky.
本综述旨在强调晚期肾细胞癌治疗方面的最新变化，这是一个复杂且不断变化的研究领域。
最近一项关于联合治疗的荟萃分析表明，纳武利尤单抗联合卡博替尼是双药治疗中总生存期的领先者。首次三联治疗试验的初步结果表明，无进展生存期优于目前的标准治疗。缺氧诱导因子-2α（HIF-2α）抑制剂贝伐珠单抗已获美国食品药品监督管理局（FDA）批准用于希佩尔-林道综合征患者，目前正在对非遗传性肾细胞癌患者进行研究。新的谷氨酸合成抑制剂替拉那司他与依维莫司联合使用可能具有协同作用，但与卡博替尼联合使用效果并不理想。双重哺乳动物雷帕霉素靶蛋白（mTOR）抑制剂萨帕尼西特似乎不是一种有效的治疗选择。新的生物标志物和靶点正在积极研究中。四项最近的试验研究了在辅助治疗中替代帕博利珠单抗的药物，但都没有显示出无复发生存率的改善。在联合治疗时代，细胞减瘤性肾切除术得到了回顾性数据的支持；临床试验正在招募患者。
过去一年，针对晚期肾细胞癌的治疗方法出现了一些新的方法，包括三联疗法、HIF-2α抑制剂、代谢途径抑制剂和双重 mTOR 抑制剂。帕博利珠单抗仍然是辅助治疗中唯一可用的现代疗法，细胞减瘤性肾切除术的相关问题仍存在争议。
