Impact of epidermal growth factor receptor and KRAS mutations on clinical outcomes in previously untreated non-small cell lung cancer patients: results of an online tumor registry of clinical trials.
Impact of epidermal growth factor receptor and KRAS mutations on clinical outcomes in previously untreated non-small cell lung cancer patients: results of an online tumor registry of clinical trials.
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表皮生长因子受体和KRAS突变对以前未经治疗的非小细胞肺癌患者的临床结果的影响：临床试验的在线肿瘤注册表的结果。
DOI：
10.1158/1078-0432.ccr-09-0888
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发表时间：
2009-08-15
期刊：
影响因子：
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通讯作者：
Johnson BE
中科院分区：
文献类型：
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作者：
Jackman DM;Miller VA;Cioffredi LA;Yeap BY;Jänne PA;Riely GJ;Ruiz MG;Giaccone G;Sequist LV;Johnson BE
表皮生长因子受体（EGFR）和KRAS基因型对厄洛替尼或吉非替尼治疗结果的影响仍存在争议。本研究综合了主要来自西方人群的五项试验中的患者数据，以评估EGFR和KRAS突变对使用EGFR - 酪氨酸激酶抑制剂（TKI）一线治疗的影响，并比较敏感性的临床预测因子和分子预测因子。
作为临床试验的一部分，接受厄洛替尼或吉非替尼单药治疗的初治晚期非小细胞肺癌患者，且已知EGFR突变状态，符合入选条件。患者每日接受厄洛替尼（150mg）或吉非替尼（250mg）治疗，直至疾病进展或出现不可接受的毒性。数据收集在一个设有密码保护的网络数据库中。对临床结果进行分析，以寻找基于EGFR和KRAS基因型以及临床特征的差异。
来自五项临床试验的223名患者被纳入研究。敏感性EGFR突变与67%的缓解率、11.8个月的无进展生存期（TTP）和23.9个月的总生存期相关。与L858R突变相比，外显子19缺失与更长的中位无进展生存期和总生存期相关。无论KRAS状态如何，野生型EGFR与较差的治疗结果相关（缓解率为3%；无进展生存期为3.2个月）。KRAS转换突变与颠换突变患者之间的治疗结果无差异。在选择适合考虑使用EGFR - TKI进行一线治疗的患者方面，EGFR基因型比临床特征更有效。
在晚期非小细胞肺癌患者中，EGFR突变状态与对EGFR - TKI治疗的敏感性相关。携带敏感性EGFR突变的患者应考虑一线使用厄洛替尼或吉非替尼治疗。
The impact of epidermal growth factor receptor (EGFR) and KRAS genotypes on outcomes with erlotinib or gefitinib therapy continues to be debated. This study combines patient data from five trials in predominantly Western populations to assess the impact of EGFR and KRAS mutations on first-line therapy with an EGFR–tyrosine kinase inhibitor (TKI) and compare clinical versus molecular predictors of sensitivity. Chemotherapy-naïve patients with advanced non–small cell lung cancer and known EGFR mutation status treated with erlotinib or gefitinib monotherapy as part of a clinical trial were eligible for inclusion. Patients received daily erlotinib (150 mg) or gefitinib (250 mg) until disease progression or unacceptable toxicity. Data were collected in a password-protected web database. Clinical outcomes were analyzed to look for differences based on EGFR and KRAS genotypes, as well as clinical characteristics. Patients (223) from five clinical trials were included. Sensitizing EGFR mutations were associated with a 67% response rate, time to progression (TTP) of 11.8 months, and overall survival of 23.9 months. Exon 19 deletions were associated with longer median TTP and overall survival compared with L858R mutations. Wild-type EGFR was associated with poorer outcomes (response rate, 3%; TTP, 3.2 months) irrespective of KRAS status. No difference in outcome was seen between patients harboring KRAS transition versus transversion mutations. EGFR genotype was more effective than clinical characteristics at selecting appropriate patients for consideration of first-line therapy with an EGFR-TKI. EGFR mutation status is associated with sensitivity to treatment with an EGFR-TKI in patients with advanced non–small cell lung cancer. Patients harboring sensitizing EGFR mutations should be considered for first-line erlotinib or gefitinib.