Department of Pathology, Ludwig-Maximilians-University of Munich, Germany.
Department of Internal Medicine III and Comprehensive Cancer Center, Klinikum Grosshadern, Ludwig-Maximilians-University of Munich, Germany; German Cancer Consortium (DKTK), Heidelberg, Germany; German Cancer Research Center (DKFZ), Heidelberg, Germany.
Eur J Cancer. 2014 Jul;50(11):1891-9. doi: 10.1016/j.ejca.2014.04.023. Epub 2014 May 20.
The role of human equilibrative nucleoside transporter 1 (hENT1) as a predictive biomarker for gemcitabine efficacy in advanced pancreatic cancer remains unclear to date.
AIO-PK0104 was a German multicenter phase III trial comparing gemcitabine/erlotinib followed by capecitabine (GEC) with capecitabine/erlotinib followed by gemcitabine (CEG) in advanced pancreatic cancer. Archival tumour tissue from 169 of the 274 eligible study patients was available for a central and standardised immunohistochemistry staining for hENT1 expression using the SP120 rabbit monoclonal anti-hENT1 antibody. Within a retrospective translational subgroup analysis, biomarker data were correlated with efficacy end-points.
Thirty-nine out of 130 fresh-cut slides were scored as hENT1(high) (30%), whereas 91 samples were classified as hENT1(low) (70%). For the 62 patients randomised to CEG median overall survival was estimated with 6.4 months in the hENT1(low) compared to 6.9 months in the hENT1(high) subgroup (Hazard Ratio (HR) 0.88, 95% confidence interval (CI) 0.48-1.61, p=0.67). For the 68 patients randomised to GEC survival was 5.7 months in the hENT1(low) compared to 4.4 months in the hENT1(high) subgroup (HR 1.16, 95% CI 0.69-1.96, p=0.57). In 101 patients receiving gemcitabine at any time during study treatment (either within the 1st- or 2nd-line setting) hENT1(low) cases had a median overall survival of 7.5 months and hENT1(high) patients an overall survival of 4.4 months (HR 1.30, 95% CI 0.84-2.03, p=0.24), respectively.
Within this subgroup analysis from Arbeitsgemeinschaft Internistische Onkologie-pancreatic cancer (AIO-PK0104), no evidence supporting the use of hENT1 as a predictive biomarker for gemcitabine efficacy in patients with advanced pancreatic cancer was found.
人嘧啶核苷转运蛋白 1（hENT1）作为吉西他滨疗效的预测生物标志物在晚期胰腺癌中的作用尚不清楚。
AIO-PK0104 是一项德国多中心 III 期试验，比较了吉西他滨/厄洛替尼序贯卡培他滨（GEC）与卡培他滨/厄洛替尼序贯吉西他滨（CEG）在晚期胰腺癌中的疗效。169 名符合条件的研究患者中有 130 名的新鲜组织切片可用于使用 SP120 兔单克隆抗 hENT1 抗体进行中央和标准化免疫组织化学染色以检测 hENT1 表达。在回顾性转化亚组分析中，将生物标志物数据与疗效终点相关联。
39 份新鲜切片中有 30%（39 份）被评为 hENT1（高），91 份样本被归类为 hENT1（低）（91 份）。在随机分配至 CEG 的 62 名患者中，hENT1（低）组的中位总生存期估计为 6.4 个月，而 hENT1（高）组为 6.9 个月（风险比（HR）0.88，95%置信区间（CI）0.48-1.61，p=0.67）。在随机分配至 GEC 的 68 名患者中，hENT1（低）组的生存时间为 5.7 个月，而 hENT1（高）组为 4.4 个月（HR 1.16，95%CI 0.69-1.96，p=0.57）。在 101 名患者中，在研究治疗期间的任何时间接受吉西他滨治疗（第 1 线或第 2 线治疗），hENT1（低）病例的中位总生存期为 7.5 个月，hENT1（高）病例的总生存期为 4.4 个月（HR 1.30，95%CI 0.84-2.03，p=0.24）。
在这项来自 Arbeitsgemeinschaft Internistische Onkologie-pancreatic cancer（AIO-PK0104）的亚组分析中，没有证据支持将 hENT1 用作晚期胰腺癌患者吉西他滨疗效的预测生物标志物。
