EGFR基因状态与晚期非小细胞肺癌患者一线化疗疗效的关系

Association between the Epidermal Growth Receptor Status and the Efficacy of First-line Chemotherapy in Patients with Advanced Non-small Cell Lung Cancer

背景与目的表皮生长因子受体(epidermal growth factor receptor,EGFR)基因状态是表皮生长因子受体酪氨酸激酶抑制剂(epidermal growth factor receptor tyrosine kinase inhibitor,EGFR-TKI)疗效的预测因素,但其对化疗疗效的预测作用尚不明确。本研究旨在探讨对晚期非小细胞肺癌(non-small cell lung cancer,NSCLC)患者一线化疗疗效的预测意义。方法收集首都医科大学附属北京胸科医院自2006年1月10日-2013年12月20日经组织病理学证实的181例IIIb期/IV期的NSCLC患者。分析EGFR基因状态、临床特征与化疗疗效及无疾病进展生存期(progression-free survival,PFS)之间的关系。结果 181例患者均进行了EGFR基因检测,EGFR突变患者75例(41.4%),野生型为106例(58.6%)。全部患者均接受一线化疗,客观缓解率(objective response rate,ORR)为26.0%,疾病控制率(disease control rate,DCR)为70.2%。EGFR突变患者的DCR显著高于EGFR野生型患者高(84.0%vs 60.4%,P=0.001)。亚组分析显示,19外显子缺失突变患者化疗的ORR、DCR均高于EGFR野生型患者(P值分别为0.049,0.002)。21外显子L858R突变患者的DCR高于EGFR野生型患者(P=0.010)。全部患者中,168例患者可评价PFS,中位PFS为4.3个月,其中腺癌患者PFS较鳞癌患者延长(4.7个月vs 3.0个月,P=0.036);突变患者PFS长于野生型患者(6.3个月vs 3.0个月,P=0.002);体力状况评分(performance status,PS)0-1分组患者PFS较评分为2分延长(4.4个月vs 0.7个月,P=0.016)。Cox多因素分析显示,EGFR突变是影响PFS的独立因素(HR=0.654,95%CI:0.470-0.909,P=0.012)。结论 EGFR突变是晚期NSCLC患者一线化疗PFS的预测因素。

Background and objective Status of epidermal growth factor receptor（EGFR） gene is a predictor of response to EGFR tyrosine kinase inhibitor（TKI）. However, little is know about the relationship between EGFR status and response to chemotherapy. We evaluated the prediction value of EGFR mutation status on response to first-line chemotherapy in patients with advanced non-small-cell lung cancer（NSCLC）. Methods The data of 181 patients with stage IIIb/IV NSCLC who diagnosed by histopathology from January 10, 2006 to December 20, 2013 in Beijing Chest Hospital, Capital Medical University were collected. The relationships between EGFR gene status, clinical characteristics and response and progressionfree survival（PFS） were analyzed. Results All of the 181 patients＇ EGFR statuses were determined. 75（41.4%） patients harbored EGFR-activating mutations and 106（58.6%） patients were EGFR wild-type. All patients received first-line chemotherapy. The objective response rate（ORR） was 26.0% and disease control rate（DCR） was 70.2%. Patients with EGFR-activating mutations had a higher DCR than patients with EGFR wild-type（84.0% vs 60.4%, P=0.001） did. Subgroup analysis showed that the ORR and DCR in patients with EGFR exon 19 deletions were remarkably higher than those with EGFR wild-type（P = 0.049, 0.002, respectively）. The DCR in patients with EGFR exon 21 L858 R mutation was significantly higher than that in patients with EGFR wild-type（P=0.010）. 168 patients were available for response evaluation in all of 181 patients and median PFS was 4.3 mo. The PFS of patients with adenocarcinoma was significantly higher than that patients with squamous cell carcinoma（4.7 mo vs 3.0 mo, P=0.036）. The PFS in patients harbored EGFR-activating mutations was significantly higher than that in the patients with EGFR wild-type（6.3 mo vs 3.0 mo, P=0.002）. The PFS of patients with a performance status（PS） of 0-1 was significantly higher than that in patients with a PS of 2（4.4 months vs. 0.7 months, P= 0.016）. Cox multivariate analysis indicates the EGFR-activating mutation is an independent factor affecting PFS（HR=0.654, 95%CI： 0.470-0.909, P=0.012）. Conclusion EGFR-activating mutation is a predictor for PFS of first-line chemotherapy in advanced NSCLC patients.