Significant improvements in mortality among patients with non-small cell lung cancer (NSCLC) in the USA over the past two decades have been reported based on Surveillance, Epidemiology, and End Results (SEER) data. The timing of these improvements led to suggestions that they result from the introduction of new treatments; however, few studies have directly investigated this. The aim of this study was to investigate the extent to which population level improvements in survival of advanced and/or metastatic NSCLC (admNSCLC) patients were associated with changes in treatment patterns. We utilized a de-identified database to select three cohorts of patients with admNSCLC: (1) patients with non-oncogene (EGFR/ALK/ROS1/BRAF) positive tumors, (2) patients with ALK-positive (ALK+) tumors, and (3) patients with EGFR-positive (EGFR+) tumors. All patients were diagnosed with admNSCLC between 2012 and 2019. Multivariable Cox models adjusting for baseline characteristics and receipt of targeted and immunotherapy were utilized to explore the relationship between these variables and changes in the hazard of death by calendar year in each cohort. We included 28,154 admNSCLC patients with non-oncogene positive tumors, 598 with ALK+ tumors, and 2464 with EGFR+ tumors eligible for analysis. After adjustment for differences in baseline characteristics, the hazard of death in patients who had non-oncogene positive tumors diagnosed in 2015, 2016, 2017, 2018 ,and 2019 was observed to be 12%, 11%, 17%, 20%, and 21% lower respectively than that for those diagnosed in 2012. Upon additionally adjusting for receipt of first line or second line immunotherapy, the decrease in the hazard of death by calendar year was no longer observed, suggesting improvements in survival observed over time may be explained by the introduction of these treatments. Similarly, decreases in the hazard of death were only observed in patients with ALK+ tumors diagnosed between 2017 and 2019 relative to 2012 but were no longer observed following adjustment for the use of 1st and later generation ALK inhibitors. Among patients with EGFR+ tumors, the hazard of death did not improve significantly over time. Our findings expand on the SEER data and provide additional evidence suggesting improvements in survival of patients with advanced and metastatic NSCLC over the past decade could be explained by the change in treatment patterns over this period.

中文翻译：

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创新的价值：晚期和转移性非小细胞肺癌生存改善与靶向和免疫治疗之间的关联

根据监测、流行病学和最终结果 (SEER) 数据，过去二十年美国非小细胞肺癌 (NSCLC) 患者的死亡率显着改善。这些改进的时机导致人们认为它们是由于引入新疗法而产生的。然而，很少有研究直接调查这一点。本研究的目的是调查晚期和/或转移性 NSCLC (admNSCLC) 患者的群体生存率改善与治疗模式变化的相关程度。我们利用去识别化数据库选择了三组 admNSCLC 患者：(1) 非癌基因 (EGFR/ALK/ROS1/BRAF) 阳性肿瘤患者，(2) ALK 阳性 (ALK+) 肿瘤患者，以及(3)EGFR阳性(EGFR+)肿瘤患者。所有患者在 2012 年至 2019 年间均被诊断为 admNSCLC。利用根据基线特征和接受靶向和免疫治疗进行调整的多变量 Cox 模型来探索这些变量与每个队列中日历年死亡风险变化之间的关系。我们纳入了 28,154 名患有非癌基因阳性肿瘤的 admNSCLC 患者、598 名患有 ALK+ 肿瘤的患者和 2464 名患有 EGFR+ 肿瘤的患者进行分析。调整基线特征差异后，观察到2015年、2016年、2017年、2018年和2019年诊断出的非癌基因阳性肿瘤患者的死亡风险分别为12%、11%、17%、20%和分别比 2012 年诊断的患者低 21%。在对接受一线或二线免疫治疗进行额外调整后，不再观察到日历年死亡风险的下降，这表明随着时间的推移观察到的生存率的改善可能是可以解释的通过引入这些治疗方法。同样，与 2012 年相比，仅在 2017 年至 2019 年诊断的 ALK+ 肿瘤患者中观察到死亡风险降低，但在调整第一代及后续 ALK 抑制剂的使用后不再观察到死亡风险降低。在 EGFR+ 肿瘤患者中，死亡风险并没有随着时间的推移而显着改善。我们的研究结果扩展了 SEER 数据，并提供了额外的证据，表明过去十年晚期和转移性 NSCLC 患者生存率的改善可以通过这一时期治疗模式的变化来解释。