Prospective study of gefitinib in epidermal growth factor receptor fluorescence in situ hybridization-positive/phospho-akt-positive or never smoker patients with advanced non-small-cell lung cancer:: The ONCOBELL trial
Prospective study of gefitinib in epidermal growth factor receptor fluorescence in situ hybridization-positive/phospho-akt-positive or never smoker patients with advanced non-small-cell lung cancer:: The ONCOBELL trial
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DOI：
10.1200/jco.2006.09.4300
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发表时间：
2007-06-01
影响因子：
45.3
通讯作者：
Varella-Garcia, Marileila
中科院分区：
文献类型：
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作者：
Cappuzzo, Federico;Ligorio, Claudia;Varella-Garcia, Marileila
目的在非小细胞肺癌(NSCLC)中，表皮生长因子受体(EGFR)酪氨酸激酶抑制剂敏感性的临床和生物学预测因素已经在回顾性研究中被确定，迫切需要在前瞻性试验中验证这些结果。ONCOBELL试验是一项前瞻性的II期研究，评估从不吸烟或有EGFR基因拷贝数增加或抗凋亡蛋白Akt激活的非小细胞肺癌患者对Gefitinib的敏感性。患者和方法用荧光原位杂交(FISH)检测EGFR基因拷贝数，用免疫组织化学方法评估磷酸化Akt的存在。结果从2004年11月至2006年2月，共筛选出183例患者，42例患者进入试验。我们观察到1个完全反应和19个部分反应，总应答率(FIR)为47.6%(95%CI，32.5%至62.7%)。中位缓解时间为6.1个月，中位进展时间(TTP)为6.4个月，1年生存率为64.3%，中位生存期未达。EGFR FISH阳性组的FIR显著高于阴性组(68.0%vs9.1%，P
PurposeIn non-small-cell lung cancer (NSCLC), clinical and biologic predictors for epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor sensitivity have been identified in retrospective studies, and there is urgent need to validate these results in prospective trials. The ONCOBELL trial is a prospective phase II study evaluating gefitinib sensitivity in NSCLC patients who never smoked or have increased EGFR gene copy number or activation of the antiapoptotic protein Akt.Patients and MethodsEGFR gene copy number was evaluated using fluorescence in situ hybridization (FISH), and presence of phospho-Akt was evaluated using immunohistochemistry. Additional tests included immunohistochemistry analysis of EGFR, FISH analysis of HER2, and mutation analysis of EGFR, HER2, and K-ras.ResultsFrom November 2004 to February 2006, 183 patients were screened, and 42 patients were enrolled onto the trial. We observed one complete and 19 partial responses, for an overall response rate (FIR) of 47.6% (95% Cl, 32.5% to 62.7%). Median duration of response was 6.1 months, median time to progression (TTP) was 6.4 months, 1-year survival rate was 64.3%, and median survival time was not reached. EGFR FISH-positive patients, compared with negative patients, had higher FIR (68.0% v 9.1 %, respectively; P