Wood Georgina, Grenader Tal, Nash Stephen, Adams Richard, Kaplan Richard, Fisher David, Maughan Tim, Bridgewater John
aDepartment of Oncology, University College London Hospital bCancer Research UK & UCL Cancer Trials Centre cMRC Clinical Trials Unit at UCL dUCL Cancer Institute, London, UK eInstitute of Cancer & Genetics, Cardiff University School of Medicine, Velindre Hospital, Cardiff fCRUK/MRC Oxford Institute for Radiation, Oxford, UK gOncology Institute, Shaare Zedek Medical Center, Jerusalem, Israel.
Anticancer Drugs. 2017 Jun;28(5):546-550. doi: 10.1097/CAD.0000000000000488.
The phase III Continuous or Intermittent (COIN) trial failed to show a benefit in overall survival (OS) of cetuximab in combination with chemotherapy for patients with metastatic colorectal cancer. High derived neutrophil to lymphocyte ratio (dNLR) has been shown to be prognostic in patients with metastatic colorectal cancer. The aim of this analysis is to evaluate dNLR as a predictive biomarker of the survival according to RAS and BRAF mutations status within the COIN trial. A post-hoc exploratory analysis of the COIN trial arms A and B was carried out. All patients with available white blood cell and neutrophil data were analysed. The dNLR was calculated using a formula that has previously shown predictive power in cancer patients: dNLR=ANC/(WBC-ANC). A high dNLR was defined as a value of 2.2 or more. dNLR was correlated with clinical outcomes using Kaplan-Meier and Cox regression analysis. A total of 1603 patients were assigned to the oxaliplatin-based chemotherapy (arm A, N=815) or oxaliplatin-based chemotherapy plus cetuximab (arm B, N=815) arms. There was a strong association between dNLR level and overall survival (OS) using Kaplan-Meier analysis. In all mutation groups, dNLR less than 2.2 was associated with better OS compared to dNLR of 2.2 or more. The median OS in patients with wild-type disease (dNLR<2.2 vs. dNLR≥2.2) was 22.8 versus 13.1 months [hazard ratio (HR)=1.33]; 16.9 versus 11.8 months (HR=1.36) in patients with RAS mutant tumours; and 12.6 versus 6.8 months (HR=1.67) in patients with BRAF mutant tumours. In patients with dNLR less than 2.2, the median OS was 19.2 months in arm A compared to 18.0 months in arm B (HR=1.11). Among patients with dNLR greater than or equal to 2.2, the median OS was 13.0 months in arm A compared with 13.1 months in arm B (HR=0.96). dNLR is strongly prognostic for survival in all mutation groups. dNLR does not predict for benefit from the addition of cetuximab.
III期持续或间歇（COIN）试验未能显示西妥昔单抗联合化疗对转移性结直肠癌患者的总生存期（OS）有获益。高衍生中性粒细胞与淋巴细胞比值（dNLR）已被证明可作为转移性结直肠癌患者的预后指标。本分析的目的是在COIN试验中，根据RAS和BRAF突变状态，评估dNLR作为生存预测生物标志物的价值。对COIN试验的A组和B组进行了事后探索性分析。分析了所有有可用白细胞和中性粒细胞数据的患者。dNLR使用先前已证明在癌症患者中有预测能力的公式计算：dNLR = 中性粒细胞绝对值（ANC）/（白细胞计数（WBC） - 中性粒细胞绝对值）。高dNLR定义为2.2或更高的值。使用Kaplan - Meier和Cox回归分析将dNLR与临床结局相关联。共有1603例患者被分配到基于奥沙利铂的化疗组（A组，N = 815）或基于奥沙利铂的化疗加西妥昔单抗组（B组，N = 815）。使用Kaplan - Meier分析，dNLR水平与总生存期（OS）之间存在强关联。在所有突变组中，与dNLR为2.2或更高相比，dNLR小于2.2与更好的OS相关。野生型疾病患者（dNLR < 2.2与dNLR≥2.2）的中位OS分别为22.8个月和13.1个月[风险比（HR）= 1.33]；RAS突变肿瘤患者为16.9个月和11.8个月（HR = 1.36）；BRAF突变肿瘤患者为12.6个月和6.8个月（HR = 1.67）。在dNLR小于2.2的患者中，A组的中位OS为19.2个月，而B组为18.0个月（HR = 1.11）。在dNLR大于或等于2.2的患者中，A组的中位OS为13.0个月，B组为13.1个月（HR = 0.96）。dNLR在所有突变组中对生存均有很强的预后价值。dNLR不能预测添加西妥昔单抗是否有获益。
