Ishihara Hiroki, Kondo Tsunenori, Yoshida Kazuhiko, Omae Kenji, Takagi Toshio, Iizuka Junpei, Tanabe Kazunari
Department of Urology, Kidney Center, Tokyo Women's Medical University, Shinjuku-ku, Tokyo, Japan.
Department of Urology, Kidney Center, Tokyo Women's Medical University, Shinjuku-ku, Tokyo, Japan; Department of Urology, Tokyo Women's Medical University Medical Center East, Arakawa-ku, Tokyo, Japan.
Urol Oncol. 2017 Sep;35(9):542.e1-542.e9. doi: 10.1016/j.urolonc.2017.05.014. Epub 2017 Jun 12.
The effect of response to first-line tyrosine kinase inhibitor (TKI) therapy on second-line survival in patients with metastatic renal cell carcinoma who receive second-line molecular-targeted therapy (mTT) after first-line failure remains unclear.
Sixty patients who developed disease progression after first-line TKI, without prior cytokine therapy, were enrolled. According to the median first-line time to progression (1L-TTP), patients were divided into 2 groups (i.e., short vs. long). Second-line progression-free survival (2L-PFS) and second-line overall survival (2L-OS) were defined as the time from second-line mTT initiation. Survival was calculated with the Kaplan-Meier method and compared using the log-rank test between patients with short and long 1L-PFS. Predictors for survivals were identified using Cox proportional hazards regression models.
The median 1L-TTP was 8.84 months. Thirty patients (50.0%) with short 1L-TTP (<8.84mo) had significantly shorter 2L-PFS and 2L-OS compared to patients with long 1L-TTP (2L-PFS: 4.96 vs. 10.2mo, P = 0.0002; 2L-OS: 9.6 vs. 28.0mo, P = 0.0036). Multivariable analyses for 2L-PFS and 2L-OS showed that 1L-TTP was an independent predictor both as a categorical classification (cutoff: 8.84mo) and as a continuous variable (both P<0.05). The median follow-up duration was 13.1 months (interquartile range: 6.56-24.7).
Patients who achieve a long-term response after first-line TKI therapy could have a favorable prognosis with second-line mTT.
一线酪氨酸激酶抑制剂（TKI）治疗的反应对一线治疗失败后接受二线分子靶向治疗（mTT）的转移性肾细胞癌患者二线生存的影响尚不清楚。
纳入60例一线TKI治疗后疾病进展且未接受过细胞因子治疗的患者。根据一线进展时间中位数（1L-TTP），将患者分为两组（即短与长）。二线无进展生存期（2L-PFS）和二线总生存期（2L-OS）定义为从二线mTT开始的时间。采用Kaplan-Meier法计算生存率，并使用对数秩检验比较1L-PFS短和长的患者。使用Cox比例风险回归模型确定生存预测因素。
1L-TTP中位数为8.84个月。与1L-TTP长的患者相比，30例（50.0%）1L-TTP短（<8.84个月）的患者2L-PFS和2L-OS显著缩短（2L-PFS：4.96个月对10.2个月，P = 0.0002；2L-OS：9.6个月对28.0个月，P = 0.0036）。对2L-PFS和2L-OS的多变量分析表明，1L-TTP作为分类变量（截断值：8.84个月）和连续变量均为独立预测因素（均P<0.05）。中位随访时间为13.1个月（四分位间距：6.56 - 24.7）。
一线TKI治疗后获得长期反应的患者接受二线mTT可能预后良好。
