目的:转移性或晚期非小细胞肺癌(NSCLC)患者需要进行生物标志物检测,包括,在大多数情况下,间变性淋巴瘤激酶(ALK),表皮生长因子受体(EGFR),和PD-L1,以确定靶向治疗的选择,并最佳地将免疫检查点抑制剂纳入治疗方案。我们试图研究生物标志物测试的真实世界模式,量化医师间的实践差异,并将测试与临床结果相关联。
方法:我们从一个全国性的电子健康记录数据库中提取了真实世界的数据,该数据库来自2018年至2021年间诊断为晚期NSCLC并在社区接受治疗的17,165名患者。我们使用描述性分析来分析数据,固定效应和混合效应逻辑回归模型,和比例风险模型。
结果:在所有17,165例患者中只有67%,在非鳞状,转移性NSCLC有ALK,EGFR,诊断后90天内进行PD-L1检测。诊断年份较晚(2019-2021年与2018年相比)与更高的ALK发生率相关,EGFR,和PD-L1测试;IIIB/C期疾病(与IV期相比),鳞状组织学,黑人或非裔美国人种族与较低的比率有关。医师之间的差异很大,ALK的医师之间的中位比值比(根据患者因素进行了调整)为1.78,EGFR,和PD-L1测试。非鳞状患者,如果使用所有三种生物标志物进行测试,转移性NSCLC的生存期显着延长(中位数,所有三个的364天,三个中没有一个的180天;危险比,0.67;P<.001)。
结论:生物标志物检测率在医生间差异较大的情况下似乎不够理想。测试与提高生存率相关,尽管因果关系不能从这项研究中得到证明。需要额外的工作来解决次优测试排序的根本原因。
OBJECTIVE: Patients with metastatic or advanced non-small cell lung cancer (NSCLC) need biomarker testing, including, in most cases, anaplastic lymphoma kinase (ALK), epidermal growth factor receptor (EGFR), and PD-L1, to identify options for targeted therapies and to optimally incorporate immune checkpoint inhibitors into therapeutic regimens. We sought to examine real-world patterns of biomarker testing, quantify interphysician practice variation, and correlate testing with clinical outcomes.
METHODS: We extracted real-world data from a nationwide electronic health record-derived deidentified database from 17,165 patients diagnosed with advanced NSCLC between 2018 and 2021 and receiving care in the community setting. We analyzed data using descriptive analyses, fixed- and mixed-effects logistic regression models, and proportional hazard models.
RESULTS: Only 67% of all 17,165 patients and 77% of patients with nonsquamous, metastatic NSCLC had ALK, EGFR, and PD-L1 testing within 90 days of diagnosis. Later diagnosis year (2019-2021 compared with 2018) was associated with higher rates of ALK, EGFR, and PD-L1 testing; stage IIIB/C disease (compared with stage IV), squamous histology, and Black or African American race were associated with lower rates. Interphysician variation was substantial with a median odds ratio between physicians (adjusted for patient factors) of 1.78 for ALK, EGFR, and PD-L1 testing. Patients with nonsquamous, metastatic NSCLC had significantly prolonged survival if tested with all three biomarkers (median, 364 days for all three v 180 for none of the three; hazard ratio, 0.67; P < .001).
CONCLUSIONS: Rates of biomarker testing appear suboptimal with substantial interphysician variation. Testing correlates with improved survival, although causality cannot be proven from this study. Additional work is needed to address the underlying causes of suboptimal test ordering.