Stalker Margaret, Grady Connor B, Watts Alex, Hwang Wei-Ting, Chandrasekhara Krishna, Sun Fangdi, Liu Geoffrey, Patel Devalben, Nieva Jorge, Herrmann Amanda, Marrone Kristen, Lam Vincent K, Velcheti Vamsidhar, Liu Stephen V, Bravo Montenegro Gabriela Liliana, Tompkins William, Patil Tejas, Weiss Jared, Miller Kelsey Leigh, Schwartzman William, Dowell Jonathan E, Shaverdashvili Khvaramze, Villaruz Liza, Cass Amanda, Iams Wade, Aisner Dara, Aggarwal Charu, Camidge D Ross, Sun Lova, Marmarelis Melina E
Department of Medicine, Perelman School of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
JTO Clin Res Rep. 2024 Nov 12;6(1):100765. doi: 10.1016/j.jtocrr.2024.100765. eCollection 2025 Jan.
Osimertinib is now a standard first-line (1L) therapy for EGFR-mutated (EGFRm) advanced NSCLC. We aimed to characterize patterns of therapy and longitudinal risk of brain and liver metastasis in a cohort of EGFRm NSCLC.
Patients with metastatic EGFRm NSCLC who received 1L systemic therapy at sites within the Academic Thoracic Medical Investigator's Consortium were included; demographic and clinical data including treatment patterns were described. Analyses of overall survival, time to next treatment, and incident brain and liver metastasis were performed using the Kaplan-Meier method, Cox regression, and cumulative incidence functions on patients who started 1L therapy in 2015 or later.
The full cohort included 1132 patients and the mean age of the participants was 63.4 years; among the participants, 53% were White individuals, 68% were female individuals, and 67% were nonsmokers. Among the participants, 830 patients received 1L systemic therapy in 2015 or later. The predominant first EGFR-tyrosine kinase inhibitor was erlotinib (65%) before 2018 and osimertinib (81%) after 2018. The median time to the next treatment after the start of 1L therapy was 13.9 months overall and the longest in patients receiving 1L osimertinib (28 months). In the post-2015 cohort, the baseline prevalence of brain metastasis (BM) was 54% and among patients without baseline brain metastasis, the probability of incident BM at 12, 24, and 48 months was 8%, 22%, and 44%, respectively. Development of an on-treatment brain metastasis among patients without baseline brain metastasis was associated with a 3.2 times higher risk of death.
Even in a contemporary era with prevalent osimertinib use, the baseline and longitudinal risk of BM development was high. The ongoing risk of developing BM, together with the associated survival detriment, argues for routine surveillance of the brain through magnetic resonance imaging for patients with EGFRm NSCLC, which is not currently included in the guidelines.
奥希替尼现已成为表皮生长因子受体突变（EGFRm）的晚期非小细胞肺癌（NSCLC）的标准一线治疗药物。我们旨在描述一组EGFRm NSCLC患者的治疗模式以及脑转移和肝转移的纵向风险。
纳入在学术性胸科医学研究者联盟各站点接受一线全身治疗的转移性EGFRm NSCLC患者；描述了人口统计学和临床数据，包括治疗模式。对2015年或之后开始一线治疗的患者，使用Kaplan-Meier法、Cox回归和累积发病率函数对总生存期、至下次治疗时间以及脑转移和肝转移的发生率进行分析。
整个队列包括1132例患者，参与者的平均年龄为63.4岁；参与者中，53%为白人，68%为女性，67%为非吸烟者。参与者中，830例患者在2015年或之后接受了一线全身治疗。2018年前主要的第一代表皮生长因子受体酪氨酸激酶抑制剂是厄洛替尼（65%），2018年后是奥希替尼（81%）。一线治疗开始后至下次治疗的中位时间总体为13.9个月，接受一线奥希替尼治疗的患者最长（28个月）。在2015年后的队列中，脑转移（BM）的基线患病率为54%，在无基线脑转移的患者中，12个月、24个月和48个月时发生脑转移的概率分别为8%、22%和44%。无基线脑转移的患者在治疗期间发生脑转移与死亡风险高3.2倍相关。
即使在奥希替尼广泛使用的当代，脑转移发生的基线和纵向风险仍然很高。发生脑转移的持续风险以及相关的生存损害，支持对EGFRm NSCLC患者通过磁共振成像进行脑的常规监测，而目前指南中未包括这一点。
