Fluorescence in situ hybridization subgroup analysis of TRIBUTE, a phase III trial of erlotinib plus carboplatin and paclitaxel in non-small cell lung cancer.
Fluorescence in situ hybridization subgroup analysis of TRIBUTE, a phase III trial of erlotinib plus carboplatin and paclitaxel in non-small cell lung cancer.
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DOI：
10.1158/1078-0432.ccr-08-0539
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发表时间：
2008-10-01
期刊：
影响因子：
--
通讯作者：
Bunn PA Jr
中科院分区：
文献类型：
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作者：
Hirsch FR;Varella-Garcia M;Dziadziuszko R;Xiao Y;Gajapathy S;Skokan M;Lin M;O'Neill V;Bunn PA Jr
TRIBUTE是一项III期试验，评价在卡铂和紫杉醇基础上添加厄洛替尼作为未达到改善总生存期主要终点的晚期非小细胞肺癌的一线治疗。在这里，我们评估的价值，使用表皮生长因子受体（EGFR）基因拷贝数在肿瘤活检标本，通过荧光原位杂交（FISH），作为治疗结果的预测。使用LSI EGFR SpectrumOrange/CEP 7 Spectrum-Green探针进行EGFR FISH分析。在275份样本中，245份（89.1%）通过FISH成功分析。100例（40.8%）患者为EGFR FISH（+）。无论是化疗+厄洛替尼组还是化疗+安慰剂组，FISH（+）和FISH（-）患者的中位总生存期均无差异。在FISH（+）患者中，厄洛替尼组的中位疾病进展时间（TTP）为6.3个月，安慰剂组为5.8个月（风险比，0.59; 95%置信区间，0.35-0.99; P = 0.0430）;在FISH（−）患者中，中位TTP为4.6个月vs 6.0个月（危害比，1.42; 95%可信区间，0.95-2.14; P = 0.0895;治疗交互作用检验，P = 0.007）。治疗6个月后，TTP曲线出现明显分离，有利于厄洛替尼。FISH（+）患者的客观缓解率分别为11.6%和29.8%（化疗+厄洛替尼组与化疗+安慰剂组; P = 0.0495），FISH（-）患者的客观缓解率分别为21.8%和25.4%（P = 0.6954）。FISH检测EGFR基因拷贝数不能预测生存获益。然而，在EGFR FISH（+）患者中，接受厄洛替尼治疗并在完成一线治疗后继续接受厄洛替尼治疗的患者的TTP较长。
TRIBUTE was a phase III trial evaluating the addition of erlotinib to carboplatin and paclitaxel as a first-line treatment for advanced non – small cell lung cancer that did not meet its primary end point of improving overall survival. Here, we assess the value of using epidermal growth factor receptor (EGFR) gene copy number in tumor biopsy samples, as determined by fluorescence in situ hybridization (FISH), as a predictor of treatment outcome. EGFR FISH analysis was done using LSI EGFR SpectrumOrange/CEP7 Spectrum-Green probe. Of 275 samples, 245 (89.1%) were successfully analyzed by FISH. One hundred (40.8%) of patients were EGFR FISH(+). Median overall survival was not different between FISH(+) and FISH(−) patients in either the chemotherapy+erlotinib arm or the chemotherapy+placebo arm. In FISH(+) patients, median time to progression (TTP) was 6.3 months in the erlotinib arm versus 5.8 months in the placebo arm (hazard ratio, 0.59; 95% confidence interval, 0.35–0.99; P = 0.0430); in FISH(−) patients, median TTP was 4.6 months versus 6.0 months (hazard ratio,1.42; 95%confidence interval, 0.95–2.14; P = 0.0895; treatment interaction test, P = 0.007). After 6 months of treatment, a notable separation of the TTP curves in favor of erlotinib emerged. Objective response rates were11.6% versus 29.8% in FISH(+) patients (chemotherapy+erlotinib arm versus chemotherapy+placebo arm; P = 0.0495) and 21.8% versus 25.4%, respectively, for FISH(−) patients (P = 0.6954). EGFR gene copy number by FISH did not predict survival benefit. However, among EGFR FISH(+) patients, TTP was longer in patients who received erlotinib and continued to receive it after completing first-line therapy.