Gong Jun, Gerendash Benjamin, Dizman Nazli, Khan Abrar, Pal Sumanta K
aDepartment of Medical Oncology and Experimental Therapeutics, City of Hope Comprehensive Cancer Center, Duarte, California, USAbDepartment of Internal Medicine, Istanbul Medeniyet University Goztepe Research and Training Hospital, Istanbul, Turkey.
Curr Opin Urol. 2016 Sep;26(5):439-46. doi: 10.1097/MOU.0000000000000319.
Multiple agents, including vascular endothelial growth factor (VEGF) inhibitors and mammalian target of rapamycin inhibitors have been approved over the past decade for the treatment of metastatic renal cell carcinoma (mRCC). Here, we focus on nivolumab, cabozantinib, and lenvatinib plus everolimus, agents that have recently emerged with positive clinical data leading to 'Food and Drug Administration approval or pending approval in mRCC. We also review the development of novel agents of interest showing promise in mRCC as part of combination therapy'.
Nivolumab and cabozantinib both offer improved survival over everolimus in the second-line treatment of mRCC. Lenvatinib plus everolimus has similarly shown encouraging survival benefits in a phase II trial for the second-line setting. Novel combinations in mRCC, including dual immune checkpoint blockade, VEGF and programmed death 1 inhibition, VEGF and vaccine therapy, dual angiogenic blockade, and VEGF-directed therapy with nanoparticle-containing camptothecin have shown promising activity in early-phase trials.
Multiple promising agents are available in the treatment of mRCC. The appropriate sequencing of agents in the treatment of mRCC may become further elucidated by future studies that prospectively analyze potential biomarkers to identify patients who will derive the greatest benefit from VEGF, mammalian target of rapamycin, or checkpoint inhibitors.
在过去十年中，包括血管内皮生长因子（VEGF）抑制剂和雷帕霉素靶蛋白抑制剂在内的多种药物已被批准用于治疗转移性肾细胞癌（mRCC）。在此，我们重点关注纳武单抗、卡博替尼以及乐伐替尼联合依维莫司，这些药物最近出现了积极的临床数据，从而获得了美国食品药品监督管理局（FDA）对mRCC的批准或正在等待批准。我们还回顾了作为联合治疗一部分在mRCC中显示出前景的新型药物的研发情况。
在mRCC的二线治疗中，纳武单抗和卡博替尼均比依维莫司能提高生存率。在二线治疗的II期试验中，乐伐替尼联合依维莫司同样显示出令人鼓舞的生存获益。mRCC中的新型联合治疗，包括双重免疫检查点阻断、VEGF和程序性死亡1抑制、VEGF和疫苗治疗、双重血管生成阻断以及含纳米颗粒喜树碱的VEGF靶向治疗，在早期试验中已显示出有前景的活性。
在mRCC的治疗中有多种有前景的药物。未来的研究可能会进一步阐明mRCC治疗中药物的合适序贯，这些研究将前瞻性地分析潜在生物标志物，以识别能从VEGF、雷帕霉素靶蛋白或检查点抑制剂中获得最大益处的患者。
