Division of Pulmonary Oncology, Guangdong Lung Cancer Institute, Guangdong General Hospital & Guangdong Academy of Medical Sciences, Guangzhou, PR China.
Lung Cancer. 2013 Jan;79(1):33-9. doi: 10.1016/j.lungcan.2012.09.016. Epub 2012 Oct 15.
There is no published overview of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) failure modes in advanced non-small-cell lung cancer (NSCLC). This study aimed to classify the diversity of EGFR-TKI failure, and to investigate the usefulness of clinical modes in subsequent management and prognosis.
One-hundred and twenty consecutive clinical trial patients with EGFR-TKI failure were enrolled as the training set to establish a clinical model based on clinical factors. Another 107 routine patients were enrolled as the validating set according to a Bayes discriminant analysis. EGFR mutations and c-MET amplification were analyzed. Kaplan-Meier survival analysis was used to test the differences among three clinical modes and subsequent management.
The duration of disease control, evolution of tumor burden, and clinical symptom were verified as feasible grouping variables. A correct grouping rate achieved 87.9%. The cohort was classified into three groups, as follows: 130 patients with dramatic progression, 42 with gradual progression, and 55 with local progression. Progression-free survivals (PFSs) for the dramatic progression, gradual progression, and local progression groups were 9.3, 12.9, and 9.2 months, respectively (P = 0.007). Overall survivals for the groups (OSs) were 17.1, 39.4, and 23.1 months, respectively (P < 0.001). TKI continuation was superior to switching chemotherapy in a subsequent setting for gradual progression (39.4 months vs. 17.8 months; P = 0.02). The difference of EGFR or c-MET among the three groups was not significant.
Clinical modes of EGFR-TKI failure could favor strategies for subsequent treatment and predicting a survival benefit in advanced NSCLC.
目前尚无关于表皮生长因子受体（EGFR）酪氨酸激酶抑制剂（TKI）治疗晚期非小细胞肺癌（NSCLC）失败模式的文献综述。本研究旨在对 EGFR-TKI 失败的多样性进行分类，并探讨临床模式在后续管理和预后中的作用。
连续纳入 120 例接受 EGFR-TKI 治疗失败的临床试验患者作为训练集，基于临床因素建立临床模型。根据贝叶斯判别分析纳入 107 例常规患者作为验证集。分析 EGFR 突变和 c-MET 扩增情况。采用 Kaplan-Meier 生存分析比较三种临床模式及后续管理的差异。
疾病控制持续时间、肿瘤负荷变化和临床症状被验证为可行的分组变量。正确分组率为 87.9%。该队列分为三组：130 例为急剧进展组，42 例为逐渐进展组，55 例为局部进展组。急剧进展、逐渐进展和局部进展组的无进展生存期（PFS）分别为 9.3、12.9 和 9.2 个月（P=0.007）。三组的总生存期（OS）分别为 17.1、39.4 和 23.1 个月（P<0.001）。在逐渐进展组，TKI 维持治疗优于化疗转换（39.4 个月 vs. 17.8 个月；P=0.02）。三组之间 EGFR 或 c-MET 无显著差异。
EGFR-TKI 失败的临床模式有助于制定晚期 NSCLC 患者的后续治疗策略，并预测生存获益。
