a Roche Products Ltd , Welwyn , UK.
b F. Hoffmann-La Roche AG Ltd , Basel , Switzerland.
Curr Med Res Opin. 2019 Mar;35(3):535-542. doi: 10.1080/03007995.2018.1533458. Epub 2018 Nov 9.
The anaplastic lymphoma kinase (ALK) treatment landscape is crowded following recent ALK inhibitor approvals, and updated information on real-world treatment patterns in advanced non-small-cell lung cancer (aNSCLC) with ALK rearrangement (ALK+) is needed.
This retrospective US cohort study used Flatiron Health's longitudinal electronic health record (EHR)-derived database. Patients (≥ 18 years old) diagnosed with stage IIIB/IV aNSCLC, with documented ALK rearrangement and ≥2 visits after January 1, 2011 were followed until February 28, 2016. Patients enrolled on a clinical trial or exposed to ALK inhibitors other than crizotinib or ceritinib were excluded. Treatment patterns, time and type of biomarker testing, and overall survival (OS) were analyzed.
Median age (n = 300) was 62.5 years; 55% female; 48% non-smokers; 8.7% central nervous system (CNS) metastases at diagnosis. Overall, 73% and 86% received their first ALK biomarker test before/at diagnosis, or before/during first-line treatment, respectively. In total, 90.0%, 78.1%, and 74.7% received first-, second-, and third-line therapy, respectively. Most patients received ALK-targeted treatment; 62% received crizotinib, of which 21% reported a dose reduction. Progression was the most common reason for crizotinib (78%) and ceritinib (41%) discontinuation. Median OS was 29.4 months (95% CI =24.7-39.6) overall; 27.1 months (95% CI =22.0-35.0) in patients with CNS metastases, and 36.9 months (95% CI =25.1-not reached) without.
Despite widespread crizotinib use in patients with ALK+ aNSCLC, a high proportion of patients progressed. Ongoing analyses of EHR-derived cohorts are valuable in assessing real-world testing rates and therapeutic use of ALK inhibitors.
在最近的 ALK 抑制剂获批后，间变性淋巴瘤激酶（ALK）的治疗领域变得非常拥挤，需要了解晚期非小细胞肺癌（aNSCLC）中 ALK 重排（ALK+）的真实世界治疗模式的最新信息。
这项回顾性的美国队列研究使用了 Flatiron Health 的纵向电子健康记录（EHR）衍生数据库。≥18 岁，诊断为 IIIB/IV 期 aNSCLC，有记录的 ALK 重排，且在 2011 年 1 月 1 日之后至少有 2 次就诊的患者，随访至 2016 年 2 月 28 日。排除参加临床试验或接受克唑替尼或塞瑞替尼以外的 ALK 抑制剂治疗的患者。分析了治疗模式、生物标志物检测的时间和类型以及总生存期（OS）。
中位年龄（n=300）为 62.5 岁；55%为女性；48%为不吸烟者；诊断时 8.7%有中枢神经系统（CNS）转移。总体而言，73%和 86%的患者分别在诊断前/时或一线治疗前进行了首次 ALK 生物标志物检测。共有 90.0%、78.1%和 74.7%的患者分别接受了一线、二线和三线治疗。大多数患者接受了 ALK 靶向治疗；62%接受了克唑替尼，其中 21%的患者报告了剂量减少。进展是克唑替尼（78%）和塞瑞替尼（41%）停药的最常见原因。总体中位 OS 为 29.4 个月（95%CI=24.7-39.6）；有 CNS 转移的患者为 27.1 个月（95%CI=22.0-35.0），无 CNS 转移的患者为 36.9 个月（95%CI=25.1-未达到）。
尽管 ALK+ aNSCLC 患者广泛使用克唑替尼，但仍有很高比例的患者出现进展。对 EHR 衍生队列的持续分析有助于评估真实世界中 ALK 抑制剂的检测率和治疗使用情况。
