Department of Medicine I, Medical University Vienna, Vienna, Austria.
Lancet Oncol. 2012 Jan;13(1):33-42. doi: 10.1016/S1470-2045(11)70318-7. Epub 2011 Nov 4.
Findings from the phase 3 First-Line ErbituX in lung cancer (FLEX) study showed that the addition of cetuximab to first-line chemotherapy significantly improved overall survival compared with chemotherapy alone (hazard ratio [HR] 0·871, 95% CI 0·762-0·996; p=0·044) in patients with advanced non-small-cell lung cancer (NSCLC). To define patients benefiting most from cetuximab, we studied the association of tumour EGFR expression level with clinical outcome in FLEX study patients.
We used prospectively collected tumour EGFR expression data to generate an immunohistochemistry score for FLEX study patients on a continuous scale of 0-300. We used response data to select an outcome-based discriminatory threshold immunohistochemistry score for EGFR expression of 200. Treatment outcome was analysed in patients with low (immunohistochemistry score <200) and high (≥200) tumour EGFR expression. The primary endpoint in the FLEX study was overall survival. We analysed patients from the FLEX intention-to-treat (ITT) population. The FLEX study is registered with ClinicalTrials.gov, number NCT00148798.
Tumour EGFR immunohistochemistry data were available for 1121 of 1125 (99·6%) patients from the FLEX study ITT population. High EGFR expression was scored for 345 (31%) evaluable patients and low for 776 (69%) patients. For patients in the high EGFR expression group, overall survival was longer in the chemotherapy plus cetuximab group than in the chemotherapy alone group (median 12·0 months [95% CI 10·2-15·2] vs 9·6 months [7·6-10·6]; HR 0·73, 0·58-0·93; p=0·011), with no meaningful increase in side-effects. We recorded no corresponding survival benefit for patients in the low EGFR expression group (median 9·8 months [8·9-12·2] vs 10·3 months [9·2-11·5]; HR 0·99, 0·84-1·16; p=0·88). A treatment interaction test assessing the difference in the HRs for overall survival between the EGFR expression groups suggested a predictive value for EGFR expression (p=0·044).
High EGFR expression is a tumour biomarker that can predict survival benefit from the addition of cetuximab to first-line chemotherapy in patients with advanced NSCLC. Assessment of EGFR expression could offer a personalised treatment approach in this setting.
Merck KGaA.
III 期 First-Line ErbituX in lung cancer（FLEX）研究的结果表明，与单独化疗相比，在晚期非小细胞肺癌（NSCLC）患者中，西妥昔单抗联合一线化疗可显著提高总生存期（风险比 [HR]0.871，95%CI0.762-0.996；p=0.044）。为了确定最能从西妥昔单抗治疗中获益的患者，我们研究了肿瘤 EGFR 表达水平与 FLEX 研究患者临床结局的相关性。
我们使用前瞻性收集的肿瘤 EGFR 表达数据，在 0-300 的连续范围内为 FLEX 研究患者生成免疫组织化学评分。我们使用反应数据选择基于结果的具有区分性的 EGFR 表达免疫组织化学评分截断值 200。分析 EGFR 高表达（免疫组织化学评分<200）和低表达（≥200）肿瘤患者的治疗结局。FLEX 研究的主要终点是总生存期。我们对 FLEX 研究的意向治疗（ITT）人群进行了分析。FLEX 研究在 ClinicalTrials.gov 注册，编号为 NCT00148798。
FLEX 研究 ITT 人群中 1125 例患者中有 1121 例（99.6%）可获得肿瘤 EGFR 免疫组织化学数据。345 例（31%）可评估患者的 EGFR 表达评分高，776 例（69%）患者评分低。在 EGFR 高表达组中，化疗加西妥昔单抗组的总生存期长于单纯化疗组（中位 12.0 个月[95%CI10.2-15.2]与 9.6 个月[7.6-10.6]；HR0.73，0.58-0.93；p=0.011），且副作用无明显增加。我们未发现 EGFR 低表达组患者有相应的生存获益（中位 9.8 个月[8.9-12.2]与 10.3 个月[9.2-11.5]；HR0.99，0.84-1.16；p=0.88）。评估 EGFR 表达组之间总生存期 HR 差异的治疗交互检验提示 EGFR 表达具有预测价值（p=0.044）。
高 EGFR 表达是一种肿瘤生物标志物，可预测晚期 NSCLC 患者接受西妥昔单抗联合一线化疗的生存获益。EGFR 表达评估可能为该人群提供一种个性化的治疗方法。
默克公司。
