Department of Medical Oncology, Gustave Roussy, Villejuif, France; INSERM U981, Paris Sud University, Gustave Roussy, Villejuif, France; Sage Bionetworks, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
INSERM U981, Paris Sud University, Gustave Roussy, Villejuif, France; Department of Biostatistics and Epidemiology, Gustave Roussy, Villejuif, France.
Eur Urol. 2014 Apr;65(4):713-20. doi: 10.1016/j.eururo.2013.08.010. Epub 2013 Aug 15.
Response Evaluation Criteria in Solid Tumors (RECIST) criteria may not be sufficient to evaluate the response of targeted therapies in metastatic renal cell carcinoma (mRCC). The tumor growth rate (TGR) incorporates the time between evaluations and may be adequate.
To determine how TGR is modified along the treatment sequence and is associated with outcome in mRCC patients.
DESIGN, SETTING, AND PARTICIPANTS: Medical records from all patients prospectively treated at Gustave Roussy (IGR) in the Treatment Approaches in Renal Cancer Global Evaluation Trial (TARGET) (sorafenib vs placebo, n=84) and the RECORD (everolimus vs placebo, n=43) phase 3 trials were analyzed. TGR was computed across clinically relevant periods: BEFORE treatment introduction (wash-out), UNDER (first cycle), at PROGRESSION (last cycle) and AFTER treatment discontinuation (washout). The association between TGR and outcome (overall survival [OS] and progression-free survival [PFS]) was computed in the entire TARGET cohort (n=903).
Sorafenib, everolimus, or placebo.
TGR, RECIST, OS, and PFS rates.
Although nearly all the patients (IGR) were classified as stable disease (RECIST) after the first cycle, the great majority of the patients exhibited a decrease in TGR UNDER compared with BEFORE (sorafenib: p<0.00001; everolimus: p<0.00001). In sorafenib-treated but not in everolimus-treated patients (IGR), TGR at PROGRESSION (last cycle) was still lower than TGR BEFORE (washout) (p=0.012), while TGR AFTER progression (washout) was higher than TGR at PROGRESSION (last cycle) (p=0.0012). Higher TGR (first cycle) was associated with worse PFS (hazard ratio [HR]: 3.61; 95% confidence interval [CI], 2.45-5.34) and worse OS (HR: 4.69; 95% CI, 1.54-14.39), independently from the Motzer score and from the treatment arm in the entire TARGET cohort.
Computing TGR in mRCC patients is simple and provides clinically useful information for mRCC patients: (1) TGR is independently associated with prognosis (PFS, OS), (2) TGR allows for a subtle and quantitative characterization of drug activity at the first evaluation, and (3) TGR reveals clear drug-specific profiles at progression.
实体瘤疗效评价标准（RECIST）可能不足以评估转移性肾细胞癌（mRCC）的靶向治疗反应。肿瘤生长率（TGR）纳入了评估之间的时间，可能足够了。
确定 TGR 在治疗序列中是如何变化的，并与 mRCC 患者的结局相关。
设计、地点和参与者：对 Gustave Roussy（IGR）前瞻性治疗的所有患者的病历进行分析，这些患者参加了全球肾癌治疗评估试验（TARGET）（索拉非尼与安慰剂，n=84）和 RECORD（依维莫司与安慰剂，n=43）三期试验。TGR 是在临床相关时期计算的：治疗前（洗脱期），治疗中（第一周期），进展时（最后一个周期）和治疗停止后（洗脱期）。在整个 TARGET 队列（n=903）中计算了 TGR 与结局（总生存期[OS]和无进展生存期[PFS]）之间的关联。
索拉非尼、依维莫司或安慰剂。
TGR、RECIST、OS 和 PFS 率。
尽管几乎所有的患者（IGR）在第一个周期后都被归类为疾病稳定（RECIST），但绝大多数患者的 TGR 在治疗中（UNDER）比治疗前（BEFORE）下降（索拉非尼：p<0.00001；依维莫司：p<0.00001）。在接受索拉非尼治疗但未接受依维莫司治疗的患者（IGR）中，进展时（最后一个周期）的 TGR 仍低于治疗前（洗脱期）（p=0.012），而进展后（洗脱期）的 TGR 高于进展时（最后一个周期）（p=0.0012）。较高的 TGR（第一周期）与较差的 PFS（危险比[HR]：3.61；95%置信区间[CI]：2.45-5.34）和较差的 OS（HR：4.69；95% CI，1.54-14.39）相关，与 Motzer 评分和整个 TARGET 队列中的治疗臂无关。
在 mRCC 患者中计算 TGR 很简单，并为 mRCC 患者提供了有临床意义的信息：（1）TGR 与预后（PFS、OS）独立相关；（2）TGR 允许在第一次评估时对药物活性进行微妙和定量的描述；（3）TGR 在进展时揭示了明确的药物特异性特征。
