INTRODUCTION Several obstacles may delay receipt of targeted treatment in patients with anaplastic lymphoma kinase positive (ALK+) non-small-cell lung cancer (NSCLC). This study examined the factors associated with delayed initiation of ALK inhibitor (ALKi) treatment and its impact on overall survival (OS) as well as the impact of initiating chemotherapy before biomarker test results. MATERIALS AND METHODS Advanced NSCLC (aNSCLC) patients selected from the deidentified Flatiron Health electronic health record-derived database were stratified into early- and delayed-use cohorts based on initiation of ALKi treatment relative to time since receiving ALK+ biomarker test results; cohorts were further stratified by timing of chemotherapy initiation relative to availability of ALK+ test results. Prescription-time matching (PTM) was used to examine the effect of delayed ALKi treatment and chemotherapy on survival; Cox proportional hazards models adjusting for baseline characteristics before and after PTM were used to examine factors associated with delayed ALKi treatment and the effects of delayed ALKi treatment and chemotherapy on OS, respectively. RESULTS Comparison of OS between early- and delayed-use cohorts (N = 442 ALK + aNSCLC patients) demonstrated that a >3-week delay in the initiation of ALKi treatment was associated with a >2-fold higher risk of death (adjusted hazard ratio [HR] [95 % CI] 2.05 [1.13, 3.71]. The number of office visits, age factors, and use of chemotherapy were associated with an increased risk of being untreated >3 weeks after ALK+ test results. There were no significant differences in survival outcomes regardless of whether patients received chemotherapy before the ALK+ test result or ALKi treatment (adjusted HR [95 % CI] 1.02 [0.64, 1.63]). Completing the chemotherapy regimen after receiving ALK+ test results did not appear to improve survival (adjusted HR [95 % CI] 0.84 [0.38, 1.9]). CONCLUSION Initiating ALKi treatment for aNSCLC patients in a timely manner may have a positive impact on survival outcomes.

中文翻译：

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延迟启动间变性淋巴瘤激酶抑制剂治疗对晚期非小细胞肺癌患者生存的影响。

引言间变性淋巴瘤激酶阳性（ALK +）非小细胞肺癌（NSCLC）患者可能会延迟接受靶向治疗。这项研究在生物标志物测试结果之前检查了与ALK抑制剂（ALKi）治疗延迟启动有关的因素及其对总生存期（OS）的影响以及启动化疗的影响。材料和方法从不明确的Flatiron Health电子健康记录数据库中选择的晚期NSCLC（aNSCLC）患者，根据自接受ALK +生物标志物检测结果以来相对于时间的ALKi治疗开始时间，分为早期和延迟使用队列。相对于ALK +测试结果的可获得性，通过化疗开始的时间进一步对这些人群进行分层。处方时间匹配（PTM）用于检查ALKi延迟治疗和化疗对生存的影响；使用Cox比例风险模型对PTM前后的基线特征进行了调整，以分别检查与延迟ALKi治疗相关的因素以及延迟ALKi治疗和化疗对OS的影响。结果早期和延迟使用的队列（N = 442名ALK + aNSCLC患者）之间的OS比较表明，ALKi治疗开始延迟> 3周与死亡风险增加> 2倍相关（调整后的危险）比率[HR] [95％CI] 2.05 [1.13，3.71]。上门服务的次数，年龄因素和化学疗法的使用与ALK +测试结果后> 3周未经治疗的风险增加相关。无论患者在ALK +测试结果之前还是在ALKi治疗之前接受化学疗法，生存结局均无显着差异（校正后HR [95％CI] 1.02 [0.64，1.63]）。接受ALK +测试结果后完成化疗方案似乎不能提高生存率（调整后的HR [95％CI] 0.84 [0.38，1.9]）。结论及时对aNSCLC患者进行ALKi治疗可能对生存结果产生积极影响。