Florida Precision Oncology, a division of 21st Century Oncology, Boca Raton, Florida, USA.
Millennium Pharmaceuticals, Inc., Cambridge, Massachusetts, USA.
Oncologist. 2020 Oct;25(10):867-877. doi: 10.1634/theoncologist.2020-0011. Epub 2020 Jul 23.
Little is known about real-world treatment and outcomes of patients with anaplastic lymphoma kinase-positive (ALK+) advanced non-small cell lung cancer (NSCLC).
This retrospective study of the Flatiron Health EHR-derived deidentified database included patients with a lung cancer diagnosis and confirmed advanced NSCLC who received ALK tyrosine kinase inhibitor (TKI) therapy (January 1, 2011, through June 30, 2018). Patient characteristics and treatment patterns were characterized. Real-world progression-free survival (rwPFS) and time to discontinuation were calculated using the Kaplan-Meier method.
First-line ALK TKI therapy was administered to 581 patients (27.5% had brain metastasis on or prior to initiation) and second-line ALK TKI therapy to 254 patients post crizotinib (45.7% had brain metastasis on or prior to second-line ALK TKI initiation). Crizotinib (84.6%; n = 492) was the most commonly administered first-line ALK TKI therapy. For second-line ALK TKI post crizotinib (n = 254), 49.6% received ceritinib, 41.7% received alectinib, 5.9% received crizotinib retreatment, and 2.8% received brigatinib. Median (95% confidence interval [CI]) rwPFS was 7.47 (6.48-8.32) months for first-line and 7.30 (5.72-8.42) months for second-line ALK TKI. Median (95% CI) rwPFS was significantly longer among first-line ALK TKI patients without than with brain metastasis (8.52 [7.57-10.59] vs. 4.97 [3.75-5.99] months; p < .0001) and patients with brain metastasis on or prior to first-line ALK TKI therapy had a significantly increased risk of progression (hazard ratio ± SE, 1.976 ± 0.112; p < .0001).
Median rwPFS in patients with advanced ALK+ NSCLC was < 8 months for first- and second-line ALK TKI therapy and was even shorter in patients with brain metastasis, highlighting the need for more effective treatments in this patient population.
Results presented herein describe real-world treatment of advanced ALK+ NSCLC with ALK TKI therapies from January 2011 through June 2018. Crizotinib was the most commonly prescribed first-line ALK TKI therapy in this patient population, but the majority of data analyzed were obtained prior to Food and Drug Administration approval of alectinib and ceritinib in the first-line ALK TKI setting. Physicians should monitor patients closely to help identify when a change in treatment should occur.
对于间变性淋巴瘤激酶阳性（ALK+）晚期非小细胞肺癌（NSCLC）患者的真实世界治疗和结局，人们知之甚少。
这项回顾性研究使用了 Flatiron Health 电子病历（EHR）衍生的去标识数据库，纳入了 2011 年 1 月 1 日至 2018 年 6 月 30 日期间被诊断患有肺癌且确诊为晚期 NSCLC 并接受 ALK 酪氨酸激酶抑制剂（TKI）治疗的患者。对患者特征和治疗模式进行了描述。采用 Kaplan-Meier 法计算真实世界无进展生存期（rwPFS）和停药时间。
581 例患者接受了一线 ALK TKI 治疗（27.5%在开始治疗时或之前有脑转移），254 例患者接受了克唑替尼后的二线 ALK TKI 治疗（45.7%在开始二线 ALK TKI 治疗时或之前有脑转移）。克唑替尼（84.6%；n=492）是最常使用的一线 ALK TKI 治疗药物。对于克唑替尼后的二线 ALK TKI 治疗（n=254），49.6%的患者接受了塞瑞替尼治疗，41.7%的患者接受了阿来替尼治疗，5.9%的患者接受了克唑替尼再治疗，2.8%的患者接受了布加替尼治疗。一线 ALK TKI 治疗的中位（95%置信区间[CI]）rwPFS 为 7.47（6.48-8.32）个月，二线 ALK TKI 治疗的中位 rwPFS 为 7.30（5.72-8.42）个月。无脑转移的一线 ALK TKI 治疗患者的中位 rwPFS 明显长于有脑转移的患者（8.52[7.57-10.59] vs. 4.97[3.75-5.99]个月；p<0.0001），且一线 ALK TKI 治疗时或之前有脑转移的患者进展风险显著增加（风险比±标准误，1.976±0.112；p<0.0001）。
ALK+晚期 NSCLC 患者一线和二线 ALK TKI 治疗的中位 rwPFS 均<8 个月，且有脑转移的患者 rwPFS 更短，这突显了该患者人群需要更有效的治疗方法。
本文介绍了 2011 年 1 月至 2018 年 6 月期间，使用 ALK TKI 治疗晚期 ALK+ NSCLC 的真实世界治疗情况。在该患者人群中，克唑替尼是最常开的一线 ALK TKI 治疗药物，但分析的大部分数据是在阿来替尼和塞瑞替尼在一线 ALK TKI 治疗环境中获得 FDA 批准之前获得的。医生应密切监测患者，以帮助确定何时应改变治疗方案。
