回顾使用基于表皮生长因子受体（EGFR）抑制剂方案治疗晚期非小细胞肺癌患者的临床试验：MD安德森癌症中心I期人群的回顾性分析
Revisiting clinical trials using EGFR inhibitor-based regimens in patients with advanced non-small cell lung cancer: a retrospective analysis of an MD Anderson Cancer Center phase I population.
作者信息
Wheler Jennifer, Falchook Gerald, Tsimberidou Apostolia M, Hong David, Naing Aung, Piha-Paul Sarina, Chen Su S, Heymach John, Fu Siqing, Stephen Bettzy, Fok Jansina Y, Janku Filip, Kurzrock Razelle
机构信息
Department of Investigational Cancer Therapeutics-Phase I Clinical Trials Program, The University of Texas MD Anderson Cancer Center, Texas, USA.
出版信息
Oncotarget. 2013 May;4(5):772-84. doi: 10.18632/oncotarget.1028.
PURPOSE
Single-agent EGFR inhibitor therapy is effective mainly in patients with lung cancer and EGFR mutations. Treating patients who develop resistance, or who are insensitive from the outset, often because of resistant mutations, other aberrations or the lack of an EGFR mutation, probably requires rational combinations. We therefore investigated the outcome of EGFR inhibitor-based combination regimens in patients with heavily-pretreated non-small cell lung cancer (NSCLC) referred to a Phase I Clinic.
METHODS
We reviewed the electronic records of patients with NSCLC treated with an EGFR inhibitor-based combination regimen: erlotinib and cetuximab; erlotinib, cetuximab and bevacizumab; erlotinib and dasatinib; erlotinib and bortezomib; or cetuximab and sirolimus.
RESULTS
EGFR mutations were detected in 16% of patients (21/131). EGFR inhibitor-based combination regimens were administered to 15 patients with EGFR-mutant NSCLC and 24 with EGFR wild-type disease. Stable disease (SD) ≥6 months/partial remission (PR) was attained in 20% of EGFR-mutant patients (3/15; two with sensitive mutations and secondary resistance to prior erlotinib, and one with a resistant mutation), as well as 26% of evaluable patients (5/19) with wild-type disease. One of three evaluable patients with squamous cell histology achieved SD for 26.5 months (EGFR wild-type, TP53-mutant, regimen=erlotinib, cetuximab and bevacizumab).
CONCLUSIONS
Eight of 34 evaluable patients (24%) with advanced, refractory NSCLC evaluable for response achieved SD ≥6 months/PR (PR=3; SD ≥6 months=5) on EGFR inhibitor-based combination regimens (erlotinib, cetuximab; erlotinib, cetuximab and bevacizumab; and, erlotinib, bortezomib), including patients with secondary resistance to single-agent EGFR inhibitors, resistant mutations, wild-type disease, and, squamous histology.
目的
单药表皮生长因子受体（EGFR）抑制剂治疗主要对肺癌且有EGFR突变的患者有效。治疗那些出现耐药的患者，或从一开始就不敏感的患者，通常是因为耐药突变、其他异常或缺乏EGFR突变，可能需要合理的联合用药。因此，我们调查了在一期临床诊所就诊的、经过大量预处理的非小细胞肺癌（NSCLC）患者中，基于EGFR抑制剂的联合治疗方案的疗效。
方法
我们回顾了接受基于EGFR抑制剂联合治疗方案的NSCLC患者的电子记录：厄洛替尼和西妥昔单抗；厄洛替尼、西妥昔单抗和贝伐单抗；厄洛替尼和达沙替尼；厄洛替尼和硼替佐米；或西妥昔单抗和西罗莫司。
结果
16%的患者（21/131）检测到EGFR突变。基于EGFR抑制剂的联合治疗方案应用于15例EGFR突变的NSCLC患者和24例EGFR野生型疾病患者。20%的EGFR突变患者（3/15；2例有敏感突变且对先前的厄洛替尼继发耐药，1例有耐药突变）以及26%的可评估的野生型疾病患者（5/19）达到了疾病稳定（SD）≥6个月/部分缓解（PR）。3例可评估的鳞状细胞组织学患者中有1例达到了26.5个月的疾病稳定（EGFR野生型，TP53突变，治疗方案=厄洛替尼、西妥昔单抗和贝伐单抗）。
结论
在34例可评估疗效的晚期难治性NSCLC患者中，8例（24%）接受基于EGFR抑制剂的联合治疗方案（厄洛替尼、西妥昔单抗；厄洛替尼、西妥昔单抗和贝伐单抗；以及厄洛替尼、硼替佐米）后达到了SD≥6个月/PR（PR=3；SD≥6个月=5），包括对单药EGFR抑制剂继发耐药、有耐药突变、野生型疾病以及鳞状组织学的患者。
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