Erlotinib for frontline treatment of advanced non-small cell lung cancer: a phase II study
Erlotinib for frontline treatment of advanced non-small cell lung cancer: a phase II study
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DOI：
10.1158/1078-0432.ccr-06-0260
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发表时间：
2006-10-15
影响因子：
11.5
通讯作者：
Soria, Jean-Charles
中科院分区：
文献类型：
--
作者：
Giaccone, Giuseppe;Ruiz, Marielle Gallegos;Soria, Jean-Charles
目的：厄洛替尼已被证明在预治疗的晚期非小细胞肺癌（NSCLC）患者中具有活性。我们评估厄洛替尼在一线治疗晚期NSCLC和评估生物学预测outcome.Experimental Design：在这第二阶段研究，化疗初治患者IIIB/IV期NSCLC接受口服厄洛替尼（150毫克/天），直到疾病进展或不可接受的毒性发生。每6周评估一次肿瘤反应，并分析样品的治疗反应和存活的潜在分子标志物。主要终点是治疗6周后无疾病进展的患者比例。6周时的总体无进展率为52.8%（53例患者中的28例）。肿瘤缓解率为22.7%，其中1例完全缓解，11例部分缓解，16例疾病稳定。在大多数患者临床特征中观察到缓解。中位肿瘤缓解持续时间为333天;中位总生存期为391天;中位疾病进展时间为84天。厄洛替尼的耐受性良好，主要的治疗相关不良事件是轻度至中度皮疹和腹泻。在29例病例中可获得用于生物学研究的组织学材料。五个应答者中的四个和一个病情稳定的患者有典型的表皮生长因子受体酪氨酸激酶突变。两个进展患者表现出表皮生长因子受体点突变（T790 M突变），和K-ras突变检测10 nonresponders.Conclusions：厄洛替尼显示出显着的抗肿瘤活性在一线治疗晚期NSCLC，可能是一个可行的替代化疗。患者的选择不能轻易地基于临床或生物学变量。
Purpose: Erlotinib has proven activity in pretreated patients with advanced non-small cell lung cancer (NSCLC). We evaluated erlotinib in the frontline treatment of advanced NSCLC and assessed biological predictors of outcome.Experimental Design: In this phase II study, chemotherapy-naive patients with stage IIIB/IV NSCLC received oral erlotinib (150 mg/d) until disease progression or unacceptable toxicity occurred. Tumor response was assessed every 6 weeks, and samples were analyzed' for potential molecular markers of treatment response and survival. The primary end point was the proportion of patients without disease progression after 6 weeks of treatment.Results: Fifty-three patients were eligible. The overall rate of nonprogression at 6 weeks was 52.8% (28 of 53 patients). Tumor response rate was 22.7%, with 1 complete response, 11 partial responses, and 16 cases of stable disease. Responses were seen across most patient clinical characteristics. The median duration of tumor response was 333 days; median overall survival was 391 days; and median time to disease progression was 84 days. Erlotinib was well tolerated, the main treatment-related adverse events being mild-to-moderate rash and diarrhea. Histologic material for biological studies was available in 29 cases. Four of five responders and one patient with stable disease had a classic epidermal growth factor receptor tyrosine kinase mutation. Two progressing patients exhibited epidermal growth factor receptor point mutations (one with T790 M mutation), and K-ras mutations were detected in 10 nonresponders.Conclusions: Erlotinib shows significant antitumor activity in the first-line treatment of advanced NSCLC and may be a viable alternative to chemotherapy. Patient selection cannot easily be based on clinical or biological variables.