Molecular characteristics of bronchioloalveolar carcinoma and adenocarcinoma, bronchioloalveolar carcinoma subtype, predict response to erlotinib
Molecular characteristics of bronchioloalveolar carcinoma and adenocarcinoma, bronchioloalveolar carcinoma subtype, predict response to erlotinib
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DOI：
10.1200/jco.2007.13.0062
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发表时间：
2008-03-20
影响因子：
45.3
通讯作者：
Johnson, David H.
中科院分区：
文献类型：
--
作者：
Miller, Vincent A.;Riely, Gregory J.;Johnson, David H.
PurposeWe进行了这个II期试验，以确定厄洛替尼在细支气管肺泡癌（BAC）和腺癌，BAC亚型的患者的疗效，并确定与response.Patients和MethodsPatients（n = 101）BAC（n = 12）或腺癌，BAC亚型（n = 89）相关的分子特征，入选。所有患者均接受厄洛替尼150 mg/d。在可用肿瘤中分析表皮生长因子受体（EGFR）突变、EGFR拷贝数、EGFR免疫组化（IHC）和KRAS突变状态。结果总有效率为2 2%（95% CI，14%~ 31%）。单纯BAC组的RR和中位生存期分别为20%和4个月，而腺癌组的RR和中位生存期分别为23%和19个月。肿瘤携带KRAS突变的患者（0/18; 95% CI，0%-19%）对厄洛替尼无应答。EGFR突变患者的RR为83%（15/18; 95% CI，65%-94%），中位OS为23个月。单变量分析显示，EGFR突变和拷贝数与RR和PFS相关。EGFR IHC与RR或无进展生存期（PFS）无关。经多因素分析，只有EGFR突变与RR和PFS相关。无分子因素与总生存率相关。结论厄洛替尼在BAC和腺癌，混合亚型，BAC中有活性。EGFR和KRAS突变检测可以预测厄洛替尼治疗非小细胞肺癌（NSCLC）患者的RR和PFS。这些数据表明，组织学亚型和分子特征应报告在临床试验中使用EGFR导向治疗的NSCLC。
PurposeWe conducted this phase II trial to determine the efficacy of erlotinib in patients with bronchioloalveolar carcinoma (BAC) and adenocarcinoma, BAC subtype, and to determine molecular characteristics associated with response.Patients and MethodsPatients (n = 101) with BAC (n = 12) or adenocarcinoma, BAC subtype (n = 89), were enrolled. All patients received erlotinib 150 mg daily. Epidermal growth factor receptor (EGFR) mutation, EGFR copy number, EGFR immunohistochemistry (IHC), and KRAS mutation status were analyzed in available tumors. The primary end point was response rate (RR).ResultsOverall RR was 22% (95% CI, 14% to 31%). In patients with pure BAC, the RR and median survival were 20% and 4 months, as compared with 23% and 19 months in those with adenocarcinoma, BAC subtype. No patient (zero of 18; 95% CI, 0% to 19%) whose tumor harbored a KRAS mutation responded to erlotinib. Patients with EGFR mutations had an 83% RR (15 of 18; 95% CI, 65% to 94%) and 23-month median OS. On univariate analysis, EGFR mutation and copy number were associated with RR and PFS. EGFR IHC was not associated with RR or progression-free survival (PFS). After multivariate analysis, only EGFR mutation was associated with RR and PFS. No molecular factors were associated with overall survival.ConclusionErlotinib is active in BAC and adenocarcinoma, mixed subtype, BAC. Testing for EGFR and KRAS mutations can predict RR and PFS after treatment with erlotinib in this histologically enriched subset of patients with non-small-cell lung cancer (NSCLC). These data suggest that histologic subtype and molecular characteristics should be reported in clinical trials in NSCLC using EGFR-directed therapy.