TKI耐药后晚期EGFR突变型非小细胞肺癌对不同治疗的反应及预测性标志物的研究

  目的  评估TKI耐药后晚期EGFR突变型非小细胞肺癌（non-small cell lung cancer，NSCLC）在真实世界中化疗、化疗联合抗血管和免疫治疗的临床疗效以及最佳免疫治疗联合方案和探讨优势人群临床病理特征。  方法  回顾性分析2014年1月至2022年10月于广东省人民医院肿瘤医院收治229例TKI耐药后晚期EGFR突变型NSCLC患者的临床病理资料。本研究将纳入的患者分为非ICI治疗组（化疗和化疗联合抗血管）122例，ICI治疗组（含免疫治疗）107例，分析患者临床特征与治疗疗效之间的关系。  结果  纳入患者非ICI治疗组和ICI治疗组的中位无进展生存期（progression-free survival，PFS）分别为5.2个月和5.2个月（P=0.129），中位生存期（overall survival，OS）分别为18.2个月和14.1个月（P=0.026）。进一步分析107例ICI治疗组，使用化疗联合免疫治疗、化疗联合抗血管联合免疫治疗和免疫单药或抗血管联合免疫治疗的中位PFS分别为5.6、6.7和2.3个月（P=0.074），中位OS分别为15.5、18.6和8个月（P=0.165）。PD-L1表达≥50%患者的中位PFS和中位OS较PD-L1表达<50%患者明显延长（中位PFS:5.6个月vs. 5.0个月，P=0.040；中位OS:19.2个月vs. 12.6个月，P=0.046）。  结论  晚期EGFR突变型NSCLC患者TKI耐药后四药联合免疫治疗似乎呈现出更好的生存获益趋势，PD-L1表达是预测该人群免疫治疗获益的生物标志物。 

Responses to different therapies and the predictive markers of advancedEGFR-mutated non-small cell lung cancer after TKI resistance

  Objective  To evaluate the clinical efficacy of chemotherapy, chemotherapy combined with anti-angiogenesis therapy, and immunotherapy in advanced EGFR-mutant non-small cell lung cancer (NSCLC) after tyrosine kinase inhibitor (TKI) resistance in clinical practice and to explore the optimal immunotherapy combination and clinicopathological characteristics of the dominant population.   Methods  Data were collected from 229 patients with advanced EGFR-mutated NSCLC who developed resistance to EGFR-TKI treatment at the Cancer Hospital of Guangdong Provincial People's Hospital from January 2014 to October 2022. One hundred and twenty-two cases of the enrolled patients were assigned into non-ICI treatment group (chemotherapy and chemotherapy combined with anti-angiogenesis therapy) and 107 cases in the ICI treatment group (including immunotherapy). The association between clinical characteristics and treatment responses were retrospectively analyzed.   Results  The median progression-free survival (PFS) of the non-ICI group (n=122) and the ICI group (n=107) were 5.2 months and 5.2 months, respectively (P=0.129). The median overall survival (OS) was 18.2 months and 14.1 months, respectively (P=0.026). Additional analysis of 107 patients treated with immunotherapy showed that the median PFS of chemotherapy combined with immunotherapy, chemotherapy combined with anti-vascular plus immunotherapy, and immune monotherapy or anti-vascular therapy combined with immunotherapy were 5.6 months, 6.7 months, and 2.3 months, respectively (P=0.074). The median OS was 15.5 months, 18.6 months, and 8 months, respectively (P=0.165). The median PFS and OS of patients with PD-L1 expression ≥50% were significantly longer than those with PD-L1 expression <50% (median PFS: 5.6 months vs. 5.0 months, P=0.040; median OS: 19.2 months vs. 12.6 months, P=0.046).   Conclusions  The four-drug combination immunotherapy provided a better survival benefit trend in patients with advanced EGFR-mutant NSCLC after TKI resistance. Furthermore, PD-L1 expression may be used as a biomarker for predicting the benefit of immunotherapy in this population.