Department of Urology, Charité University Medicine Berlin, Berlin, Germany.
Eur Urol. 2011 Dec;60(6):1163-70. doi: 10.1016/j.eururo.2011.07.037. Epub 2011 Jul 21.
The best sequence of targeted therapy in patients with metastatic renal cell carcinoma (mRCC) has not been sufficiently defined.
To describe the efficacy and toxicity of sequential everolimus (EV) versus receptor tyrosine kinase inhibitor (rTKI) following failure of first rTKI treatment.
DESIGN, SETTING, AND PARTICIPANTS: Retrospective study of 108 patients receiving rTKI or EV after progression on rTKI therapy at two German academic centres.
Sequence of systemic targeted treatment with sunitinib (n=85) or sorafenib (n=23) followed by EV (n=62) or another rTKI (n=46; sorafenib, n=35; sunitinib, n=11).
We measured response rate (Response Evaluation Criteria in Solid Tumours 1.0) and toxicity. Survival analysis (Kaplan-Meier method and Cox regression) was conducted for progression-free survival (PFS) and overall survival (OS).
Main patient characteristics did not significantly differ by sequence of treatment groups (rTKI-rTKI vs rTKI-EV). Response rate following first rTKI failure was not significantly different between sequential therapies with a disease control rate of 51.6% (EV) and 43.5% (rTKI). The corresponding median PFS was 3.6 mo (95% confidence interval [CI], 1.8-5.4) for EV and 4.0 mo (3.2-4.9) for rTKI treatment. The estimated OS was longer for the rTKI-EV group (43 mo; 95% CI, 33.9-52.1) than for the rTKI-rTKI group (29 mo; 95% CI, 18.6-39.5; p=0.03), but this difference lost statistical significance in multivariable-adjusted analyses. Intrinsic rTKI resistance was independently associated with inferior subsequent PFS (hazard ratio [HR]: 1.79; 95% CI, 1.15-3.62; p=0.015) and OS (HR: 6.54; 95% CI, 3.01-14.20; p<0.001). Limitations are the retrospective design, limited numbers of cases, and residual confounding factors.
The sequence therapies rTKI-EV and rTKI-rTKI may be equally efficacious in terms of PFS and response rate, whereas a tendency towards superior survival was observed for the rTKI-EV sequence. These data, particularly the potential benefit of an early change of mode of action, need confirmation in randomised comparative trials.
转移性肾细胞癌（mRCC）患者的最佳靶向治疗序列尚未得到充分明确。
描述依维莫司（EV）序贯治疗在接受第一代受体酪氨酸激酶抑制剂（rTKI）治疗后进展的转移性肾细胞癌患者中的疗效和毒性。
设计、地点和参与者：在德国的两个学术中心，对 108 例接受 rTKI 或 EV 治疗的患者进行了回顾性研究，这些患者在 rTKI 治疗进展后接受了治疗。
采用舒尼替尼（n=85）或索拉非尼（n=23）序贯治疗，然后采用 EV（n=62）或另一种 rTKI（n=46；索拉非尼，n=35；舒尼替尼，n=11）。
我们测量了反应率（实体瘤反应评价标准 1.0）和毒性。无进展生存期（PFS）和总生存期（OS）采用生存分析（Kaplan-Meier 法和 Cox 回归）。
主要患者特征在治疗组的序列上无显著差异（rTKI-rTKI 与 rTKI-EV）。首次 rTKI 失败后，序贯治疗的反应率无显著差异，疾病控制率分别为 51.6%（EV）和 43.5%（rTKI）。相应的中位 PFS 分别为 EV 组 3.6 个月（95%CI，1.8-5.4）和 rTKI 组 4.0 个月（3.2-4.9）。rTKI-EV 组的估计 OS 长于 rTKI-rTKI 组（43 个月；95%CI，33.9-52.1），但在多变量调整分析中，这一差异失去了统计学意义。内在 rTKI 耐药与后续 PFS 较差（危险比[HR]：1.79；95%CI，1.15-3.62；p=0.015）和 OS 较差（HR：6.54；95%CI，3.01-14.20；p<0.001）独立相关。局限性在于回顾性设计、病例数量有限以及残留的混杂因素。
在 PFS 和反应率方面，rTKI-EV 和 rTKI-rTKI 序贯治疗可能同样有效，而 rTKI-EV 序贯治疗的生存趋势较好。这些数据，特别是早期改变作用模式的潜在益处，需要在随机对照试验中得到证实。
