Clinical Predictive Factors associated with First Line EGFR-TKI Efficacy in Advanced NSCLC Patients with EGFR Mutations

Abstract

一线应用表皮生长因子-酪氨酸激酶抑制剂（epidermal growth factor receptor tyrosine kinase inhibitors, EGFR-TKIs）治疗具有EGFR基因突变的晚期非小细胞肺癌（non-small cell lung cancer, NSCLC）疗效显著，但患者的无进展生存时间（progression free survival, PFS）可有较大差异。既往研究表明一些临床因素可能与疗效相关，本研究旨在探讨影响EGFR-TKI疗效的临床预测因素。方法 收集203例存在EGFR基因敏感突变且一线接受EGFR-TKI治疗的晚期NSCLC患者的人口学及临床资料并进行回顾性分析。结果 截至随访结束时203例患者中共有139例发生病情进展，63例死亡。中位随访时间为21.1个月，中位PFS为14.3个月。接受治疗患者疾病部分缓解（partial response, PR）127例（66.1%），疾病稳定（stable disease, SD）55例（28.6%）。与PFS相关的单因素分析结果显示，ECOG评分≥2分（5.1个月 vs 16个月，P=0.033）、最佳疗效为SD（9.5个月 vs 17.9个月，P=0.030）、合并胸腔外远处转移（11.7个月 vs 27.5个月，P=0.004）、肝转移（4.1个月 vs 16.0个月，P=0.000）、骨转移（13.3个月 vs 21.5个月，P=0.027）和同时并发肺栓塞（5.5个月 vs 16.6个月，P=0.005）的患者PFS明显缩短。多因素Cox回归结果显示合并肝转移（HR=1.694, 95%CI: 1.146-5.756, P=0.022）、最佳治疗反应仅达到SD（HR=1.825, 95%CI: 1.107-3.008, P=0.018）是独立的疗效预测因素。结论 对于EGFR突变阳性的晚期NSCLC患者，一线应用EGFR-TKI治疗效果良好。治疗的最佳疗效以及基线肝转移是PFS的独立临床预测因素。

Background and objective Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have demonstrated some dramatic efficacy in advanced non-small-cell lung cancer (NSCLC) patients with activating EGFR mutation. However, progression-free survivals (PFS) among those patients who were treated with first line EGFR TKIs were inconsistent. The aim of this study is to explore the association of clinical prognostic factors with EGFR-TKI efficacy in advanced NSCLC patients. Methods The demographic and clinical characteristics of 203 patients with activating EGFR mutation treated with first generation TKI as a first-line therapy were retrospectively reviewed. Results Of the 203 patients enrolled in this study, 139 patients had progression of disease and 63 patients died. The subjects had a median follow up duration of 21.1months and a median PFS of 14.3 months. Partial response (PR) was achieved in 127 (66.1%) patients and stable disease (SD) rate was achieved in 55 (28.6%) patients. In univariate analysis, patients with 2 or higher ECOG score (5.1 vs 16 months, P=0.033), SD as best overall response (9.5 vs 17.9 months, P=0.030), extrathoracic metastasis (11.7 vs 27.5 months, P=0.004), liver metastasis (4.1 vs 16.0 months, P=0.000), bone metastasis (13.3 vs 21.5months, P=0.027) and pulmonary embolism (5.5 vs 16.6 months, P=0.005) had shorter PFS than those without the listed factors. Multivariable Cox regression analysis showed best overall response (HR=1.825, 95%CI: 1.107-3.008, P=0.018) and liver metastasis (HR=1.694, 95%CI: 1.146-5.756, P=0.022) were independent predictive factors of shorter PFS. Conclusion Despite the high efficacy of EGFR-TKI, SD as best overall response and liver metastasis predicts poorer PFS in advanced NSCLC patients with EGFR gene mutations receiving first-line therapy treatment.