Background: Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) significantly improve the survival of advanced lung adenocarcinoma patients harboring EGFR mutation. Limited to the standards of tumor tissue samples and detection methods, still some people can't receive target therapy following genetic guidance. This study was to explore the relevance between serum tumor markers and treatment of EGFR-TKIs.
Methods: We retrospectively collected the clinical information of advanced lung adenocarcinoma patients harboring EGFR mutation, who received EGFR-TKIs as first-line therapy from June 2009 to June 2014 in Peking University Cancer Hospital, analyzed the relationship between serum tumor markers and efficacy of EGFR-TKIs.
Results: The objective response rate (ORR) was 52.8% and the disease control rate (DCR) was 89.3%. The results showed that, patients with high CEA level before treatment responded better to TKIs (ORR 61.3% vs 35.9%, DCR 95.2% vs 74.4%, P<0.001). Similar phenomena was found in patients with CEA decreased 1 month later (61.5% vs 25%, P=0.002). Progression-free survival (PFS) significantly prolonged in patients with elevated baseline CEA (mPFS 9.8 mo vs 5.9 mo, P=0.027). To the opposite, PFS was significantly shorter in patients with elevated baseline CYFRA21-1 and CA125 (mPFS 9.0 mo vs 11.4 mo, P=0.029; 9.0 mo vs 11.5 mo, P=0.023, respectively). Multivariate analysis showed that Eastern Cooperative Oncology Group (ECOG) score of 0-1, normal baseline CYFRA21-1 and CEA decline predicted longer PFS. The overall survival (OS) was highly associated with elevated CYFRA21-1 and CA125 (median OS 25.1 mo vs 52.5 mo, P=0.003; 22.7 mo vs 55.0 mo, P<0.001, respectively), while independent of CEA.
Conclusions: High level of baseline CEA and decline 1 month after treatment could predict the efficacy of EGFR-TKIs in patients with advanced lung adenocarcinoma. While high levels of baseline CYFRA21-1 and CA125 indicated shortened survival.
背景与目的 表皮生长因子受体酪氨酸激酶抑制剂（epidermal growth factor receptor tyrosine kinase inhibitors, EGFR-TKIs）在EGFR突变型肺腺癌人群中能显著提高生存，从而改变了晚期肺癌的治疗模式，但并不是所有EGFR敏感突变者均能从EGFR-TKIs治疗中获益。本研究欲通过外周血肿瘤标志物的检测对突变型肺腺癌患者的靶向治疗进行预测及指导。方法 回顾性分析2009年6月-2014年6月于北京大学肿瘤医院胸部肿瘤内一科一线接受EGFR-TKIs治疗的EGFR突变型IIIb期-IV期肺腺癌患者的临床资料，分析其基线肿瘤标志物与EGFR-TKIs疗效及生存的关系。结果 总体人群客观有效率（objective response rate, ORR）52.8%，疾病控制率（disease control rate, DCR）89.3%。基线癌胚抗原（carcino-embryonic antigen, CEA）水平升高者对EGFR-TKIs疗效更佳（ORR 61.3% vs 35.9%, DCR 95.2% vs 74.4%, P<0.001），治疗1个月后CEA、细胞角蛋白19片段（cytokeratin 19 fragments, CYFRA21-1）以及CA125水平下降者有效率更高（ORR分别是61.5% vs 25%，P=0.002；58.5% vs 37.5%，P=0.004；61.8% vs 20%，P=0.027）。生存分析中，基线CEA水平正常者较高水平者无进展生存期（progression-free survival, PFS）明显缩短（中位PFS 5.9个月 vs 9.8个月，P=0.027），而基线CYFRA21-1、CA125水平升高者PFS明显缩短（中位PFS 9.0个月 vs 11.4个月，P=0.029；9.0个月 vs 11.5个月，P=0.023）。多因素分析显示，美国东部肿瘤协作组（Eastern Cooperative Oncology Group, ECOG）评分0-1分、基线CYFRA21-1正常水平、治疗1月后CEA下降阳性患者PFS更长。总生存期（overall survival, OS）与CYFRA21-1、CA125升高有关（中位OS分别为25.1个月 vs 52.5个月，P=0.003；22.7个月 vs 55.0个月，P<0.001），而多因素分析中总生存与CEA下降有关（P=0.046）。结论 治疗前高水平CEA以及治疗后CEA下降可以预测晚期肺腺癌患者一线接受EGFR-TKIs的疗效，而治疗前高水平CYFRA21-1以及CA125则预示着生存期缩短。.