Vogelzang Nicholas J, Pal Sumanta K, Signorovitch James E, Reichmann William M, Li Nanxin, Yang Chelsey, Liu Zhimei, Perez Jose Ricardo, Jonasch Eric
a US Oncology Research, Comprehensive Centers of Nevada , Las Vegas , NV , USA ;
b City of Hope Comprehensive Cancer Center , Duarte , CA , USA ;
Curr Med Res Opin. 2016;32(4):741-7. doi: 10.1185/03007995.2016.1140028. Epub 2016 Jan 25.
Background Second targeted therapies for metastatic renal cell carcinoma (mRCC) include mammalian target of rapamycin inhibitors (mTORis) and tyrosine kinase inhibitors (TKIs). This observational study compares overall survival (OS) and progression-free survival (PFS) of patients treated with everolimus (an mTORi) and axitinib (a TKI) following first TKI, and assesses the impact of type and duration of first TKI on the relative effectiveness of these second targeted therapies. Methods Retrospective reviews of medical records were conducted by medical oncologists or hematologists/oncologists recruited from a nationwide panel. Included patients with mRCC were required to have discontinued a first TKI (sunitinib, sorafenib, or pazopanib) for medical reasons, and to have initiated everolimus or axitinib as second targeted therapy between February 2012 and January 2013. OS and PFS were compared between patients treated with everolimus vs. axitinib using multivariable Cox proportional hazards regression models. Comparative results were also stratified by type and duration of first TKI. Results Included patients (n = 325 for everolimus and n = 127 for axitinib) had a mean age of 61 years and 31% were female. Sunitinib was the most commonly used first TKI (73%). After adjusting for patient characteristics, no statistically significant differences were observed in OS or PFS between everolimus and axitinib. When stratifying by type and duration of first TKI, there was no statistically significant difference in OS between everolimus and axitinib in all subgroups except for patients with <6 months on sunitinib or sorafenib as first TKI. No significant difference in PFS was observed in any subgroup. Limitations Important limitations include potential missing or inaccurate data in medical charts, and confounding due to unobserved factors. Conclusions In this retrospective chart review, no significant differences were detected in OS or PFS between axitinib and everolimus as second targeted therapy. Longer duration of first TKI was not associated with increased effectiveness of subsequent axitinib compared to everolimus.
背景 转移性肾细胞癌（mRCC）的二线靶向治疗包括雷帕霉素靶蛋白抑制剂（mTORi）和酪氨酸激酶抑制剂（TKI）。这项观察性研究比较了依维莫司（一种mTORi）和阿昔替尼（一种TKI）在一线TKI治疗后患者的总生存期（OS）和无进展生存期（PFS），并评估一线TKI的类型和持续时间对这些二线靶向治疗相对疗效的影响。方法 由从全国专家小组招募的医学肿瘤学家或血液学/肿瘤学家对病历进行回顾性审查。纳入的mRCC患者要求因医学原因停用一线TKI（舒尼替尼、索拉非尼或帕唑帕尼），并于2012年2月至2013年1月期间开始使用依维莫司或阿昔替尼作为二线靶向治疗。使用多变量Cox比例风险回归模型比较接受依维莫司与阿昔替尼治疗患者的OS和PFS。比较结果也按一线TKI的类型和持续时间进行分层。结果 纳入患者（依维莫司组n = 325，阿昔替尼组n = 127）的平均年龄为61岁，31%为女性。舒尼替尼是最常用的一线TKI（73%）。在调整患者特征后，依维莫司和阿昔替尼之间在OS或PFS方面未观察到统计学上的显著差异。当按一线TKI的类型和持续时间分层时，除了以舒尼替尼或索拉非尼作为一线TKI治疗时间<6个月的患者外，依维莫司和阿昔替尼在所有亚组中的OS均无统计学上的显著差异。在任何亚组中均未观察到PFS有显著差异。局限性 重要局限性包括病历中可能存在的数据缺失或不准确，以及未观察到的因素导致的混杂。结论 在这项回顾性病历审查中，阿昔替尼和依维莫司作为二线靶向治疗在OS或PFS方面未检测到显著差异。与依维莫司相比，一线TKI的较长持续时间与随后阿昔替尼疗效增加无关。
