驱动基因阳性且PD-L1高表达的非小细胞肺癌患者病理特征及靶向治疗疗效评估的真实世界研究

A Real-world Study on the Assessment of Pathological Characteristics and Targeted Therapeutic Effect of Non-small Cell Lung Cancer Patients with Positive Driving Genes and High PD-L1 Expression

背景与目的驱动基因突变阳性患者行靶向治疗,驱动基因阴性但程序性死亡配体1(programmed death-ligand 1,PD-L1)高表达患者行免疫抑制剂治疗,是晚期非小细胞肺癌(non-small cell lung cancer,NSCLC)患者一线治疗的首选,但对于驱动基因阳性且PD-L1高表达患者的治疗选择仍值得探究。方法以315例NSCLC患者为研究对象,分析驱动基因阳性且PD-L1高表达患者的临床病理特征及靶向治疗疗效。结果本研究纳入的315例NSCLC患者中,驱动基因突变总阳性率为62.2%,PD-L1高表达率(250.0%)为11.2%,驱动基因阳性且PD-L1高表达的患者比例为10.7%。其中表皮生长因子受体(epidermal growth factor receptor,EGFR)突变、KRAS突变、ALK融合、BRAF突变和MET 14外显子跳跃突变患者中均有PD-L1高表达,比例分别为7.8%(11/141)、18.2%(4/22)、23.1%(3/13)、50.0%(2/4)和100.0%(1/1)。EGFR突变且PD-L1高表达患者主要为Ⅳ期肺腺癌患者,KRAS突变且PD-L1高表达患者主要为有吸烟史的患者。其中详细跟踪了两例分别为ALK融合阳性且PD-L1高表达(90.0%)和EGFR L858R突变且PD-L1高表达(70.0%)患者的靶向治疗全过程,两例患者总生存期分别仅为5个月和2个月。结论NSCLC患者各驱动基因突变与PD-L1高表达共存的比例和临床病理特征有较大差异。发生敏感突变且PD-L1高表达的患者靶向治疗疗效和预后可能更差。

Background and objective Targeted therapy for patients with driver genes positive and immunotherapy for patients with driver gene-negative but high programmed death ligand 1(PD-L1)expression are the standards of firstline treatment for patients with advanced non-small cell lung cancer(NSCLC).The treatment options for patients with driver gene positive and high PD-L1 expression are still worth exploring.Methods The characteristics of 315 patients with NSCLC were identified to analyze the clinicopathological characteristics of patients with driver gene positive and high PD-L1 expression,and the efficacy of targeted therapy.Results Among the 315 patients,the total positive rate of driver genes was 62.2%,and the high PD-L1 expression rate(>50.0%)was 11.2%.The proportion of patients with driver gene positive and high PD-L1 expression was 10.7%.PD-L1 was highly expressed in patients with epidermal growth factor receptor(EGFR)mutation,KRAS mutation,ALK fiision,mutation,and MET 14 exon skip mutation,the proportions were 7.8%(11/141),18.2%(4/22),and 23.1%,(3/13),50.0%(2/4)and 100.0%(1/1)respectively.EGFR mutation positive with PD-L1 high expression was mainly in patients with stage IV lung adenocarcinoma.KRAS mutation positive with PD-L1 high expression was mainly in patients with a history of smoking.Among them,two patients were followed in detail for targeted therapy,who with ALK fusion-positive and PD-L1 high expression(90.0%),EGFR L858R mutation and PD-L1 high expression(70.0%)respectively.The total OS of the patients was 5 months,2 months.Conclusion The high PD-L1 expression rate in NSCLC patients with different driver gene mutations was variable,which maybe correlated with distinct clinicopathological characteristics.Patients with sensitive mutations and high PD-L1 expression may be less benefit from targeted therapy and have poor prognosis.