EGFR expression as a predictor of survival for first-line chemotherapy plus cetuximab in patients with advanced non-small-cell lung cancer: analysis of data from the phase 3 FLEX study
EGFR expression as a predictor of survival for first-line chemotherapy plus cetuximab in patients with advanced non-small-cell lung cancer: analysis of data from the phase 3 FLEX study
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DOI：
10.1016/s1470-2045(11)70318-7
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发表时间：
2012-01-01
期刊：
影响因子：
51.1
通讯作者：
O'Byrne, Kenneth J.
中科院分区：
文献类型：
--
作者：
Pirker, Robert;Pereira, Jose R.;O'Byrne, Kenneth J.
背景：3期一线ErbituX治疗肺癌（FLEX）研究结果显示，与单纯化疗相比，在一线化疗中加入西妥昔单抗可显著提高晚期非小细胞肺癌（NSCLC）患者的总生存率（风险比[HR] 0.871, 95% CI 0.762-0.996; p=0.044）。为了确定从西妥昔单抗中获益最多的患者，我们研究了FLEX研究患者肿瘤EGFR表达水平与临床结果的关系。方法：我们使用前瞻性收集的肿瘤EGFR表达数据，以0-300的连续评分为FLEX研究患者生成免疫组织化学评分。我们使用应答数据选择EGFR表达为200的基于结果的歧视性阈值免疫组织化学评分。对肿瘤EGFR表达低（免疫组化评分= 200）患者的治疗结果进行分析。FLEX研究的主要终点是总生存期。我们分析了来自FLEX意向治疗（ITT）人群的患者。FLEX研究已在ClinicalTrials.gov注册，注册号NCT00148798。在FLEX研究的ITT人群中，1125例（99.6%）患者中有1121例可获得肿瘤EGFR免疫组化数据。EGFR高表达345例（31%）可评估患者，低表达776例（69%）患者。对于EGFR高表达组患者，化疗加西妥昔单抗组的总生存期长于单独化疗组（中位12.0个月[95% CI 10.2-15.2] vs 9.6个月[7.6-10.6];HR 0.73, 0.58-0.93; p=0.011），副作用无显著增加。我们没有记录到低EGFR表达组患者相应的生存获益（中位9.8个月[8.9-12.2]vs 10.3个月[9.2-11.5];HR 0.99, 0.84-1.16; p=0.88）。一项评估EGFR表达组之间总生存率差异的治疗相互作用试验表明，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，可以预测晚期非小细胞肺癌患者在一线化疗中添加西妥昔单抗后的生存获益。在这种情况下，评估EGFR表达可能需要个性化的治疗方法。
Background 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.Methods 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) 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.Findings 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).Interpretation 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 off er a personalised treatment approach in this setting.