Meskawi Malek, Valdivieso Roger, Dell'Oglio Paolo, Trudeau Vincent, Larcher Alessandro, Karakiewicz Pierre I
Cancer Prognostics and Health Outcomes Unit, University of Montreal Health Center, Montreal, Quebec, Canada; Division of Oncology, Unit of Urology, URI, IRCCS Ospedale San Raffaele, Milan, Italy.
J Kidney Cancer VHL. 2015 Dec 30;2(4):187-194. doi: 10.15586/jkcvhl.2015.43. eCollection 2015.
Everolimus (RAD001) is an orally administered agent that inhibits the mammalian target of rapamycin serine-threonine kinase. A phase III pivotal trial on everolimus, published in 2008, provided the first evidence for the efficacy of sequential therapy for patients with metastatic clear cell renal cell carcinoma (RCC). In this study, everolimus was used after failure of one or several previous lines of therapy, and it demonstrated a 3-month survival benefit relative to placebo. Currently, based on the level 1 evidence, everolimus represents the molecule of choice for third-line therapy after failure of previous two tyrosine kinase inhibitors (TKIs). However, second-line use after failure of one TKI is challenged by two new molecules (nivolumab and cabozantinib), which proved to have better efficacy with similar toxicity profile. In non-clear cell metastatic RCC, the current evidence recommends everolimus as a second-line therapy after failure of previous first-line sunitinib.
依维莫司（RAD001）是一种口服制剂，可抑制雷帕霉素丝氨酸 - 苏氨酸激酶的哺乳动物靶点。2008年发表的一项关于依维莫司的III期关键试验，首次为转移性透明细胞肾细胞癌（RCC）患者序贯治疗的疗效提供了证据。在这项研究中，依维莫司在先前一线或多线治疗失败后使用，相对于安慰剂，它显示出3个月的生存获益。目前，基于一级证据，依维莫司是先前两种酪氨酸激酶抑制剂（TKIs）失败后三线治疗的首选分子。然而，一种TKI失败后的二线使用受到两种新分子（纳武单抗和卡博替尼）的挑战，这两种新分子被证明具有更好的疗效且毒性特征相似。在非透明细胞转移性RCC中，目前的证据推荐依维莫司作为先前一线舒尼替尼失败后的二线治疗。
