Tripathi Abhishek, Jacobus Susanna, Feldman Hope, Choueiri Toni K, Harshman Lauren C
Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Boston, MA.
Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA.
Clin Genitourin Cancer. 2017 Jun;15(3):396-402. doi: 10.1016/j.clgc.2016.12.009. Epub 2016 Dec 13.
Increases in hemoglobin have been reported in renal cell carcinoma (RCC) patients treated with vascular endothelial growth factor (VEGF) pathway-targeted therapies and have been associated with increased progression-free survival (PFS). We retrospectively evaluated its significance as a predictive biomarker of clinical response in RCC.
Patients with advanced RCC treated with VEGF receptor tyrosine kinase inhibitors (TKIs) or bevacizumab as a first-line therapy were identified. Hemoglobin levels were retrieved at baseline and then at monthly intervals for 6 months. Absolute and percentage increases over baseline were evaluated as predictors of objective response rate, PFS, time to treatment failure, and overall survival. Cox regression was used to estimate change status hazard ratios (HR) in univariate and multivariable models.
Among the 71 eligible patients, elevations in hemoglobin were observed in 83%, with a median time to increase of 2.4 weeks since treatment initiation. Changes in hemoglobin at time of response were not associated with objective response rate. Landmark analysis at 3 months showed that increases in hemoglobin were associated with worse PFS (8.0 vs. 19.4 months; HR = 2.29; 95% confidence interval, 1.01-5.16; P = .05) and time to treatment failure (6.4 vs. 18.1 months; HR = 2.14; 95% confidence interval, 0.99-4.60, P = .05). Patients with greater increases (15% or more) had significantly shorter PFS (5.5 vs. 13.6 months) and overall survival (20.8 vs. 30.4 months) compared to those with lesser degree of elevations.
Contrary to prior reports, elevation in hemoglobin on VEGF-directed therapy was associated with worse clinical outcomes, and the greater the degree of elevation, the poorer the prognosis.
据报道，接受血管内皮生长因子（VEGF）通路靶向治疗的肾细胞癌（RCC）患者血红蛋白水平升高，且与无进展生存期（PFS）延长相关。我们回顾性评估了其作为RCC临床反应预测生物标志物的意义。
确定接受VEGF受体酪氨酸激酶抑制剂（TKIs）或贝伐单抗作为一线治疗的晚期RCC患者。在基线时以及随后6个月每月检索血红蛋白水平。将超过基线的绝对增加量和百分比增加量评估为客观缓解率、PFS、治疗失败时间和总生存期的预测指标。使用Cox回归在单变量和多变量模型中估计变化状态风险比（HR）。
在71例符合条件的患者中，83%观察到血红蛋白升高，自治疗开始起血红蛋白升高的中位时间为2.4周。缓解时血红蛋白的变化与客观缓解率无关。3个月时的标志性分析显示，血红蛋白升高与较差的PFS（8.0个月对19.4个月；HR = 2.29；95%置信区间，1.01 - 5.16；P = 0.05）和治疗失败时间（6.4个月对18.1个月；HR = 2.14；95%置信区间，0.99 - 4.60，P = 0.05）相关。与升高程度较小的患者相比，升高幅度较大（15%或更多）的患者PFS（5.5个月对13.6个月）和总生存期（20.8个月对30.4个月）明显更短。
与先前报道相反，VEGF靶向治疗时血红蛋白升高与较差的临床结局相关，且升高程度越大，预后越差。
