Efficacy and Safety of Larotrectinib in Patients With Tropomyosin Receptor Kinase Fusion-Positive Lung Cancers.
Efficacy and Safety of Larotrectinib in Patients With Tropomyosin Receptor Kinase Fusion-Positive Lung Cancers.
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左霉素受体激酶融合融合阳性肺癌患者的洛拉托替尼的功效和安全性。
DOI：
10.1200/po.21.00418
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发表时间：
2022-01
影响因子：
4.6
通讯作者：
Lin JJ
中科院分区：
文献类型：
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作者：
Drilon A;Tan DSW;Lassen UN;Leyvraz S;Liu Y;Patel JD;Rosen L;Solomon B;Norenberg R;Dima L;Brega N;Shen L;Moreno V;Kummar S;Lin JJ
Larotrectinib是一种高选择性和CNS活性的原肌球蛋白受体激酶（TRK）抑制剂，已证明对TRK融合阳性癌症有效，无论肿瘤类型如何。本研究的目的是评估Larotrectinib在TRK融合阳性肺癌患者中的疗效和安全性。分析了来自两项全球多中心、注册临床试验的数据：一项II期成人和年轻成人网篮试验（NCT 02576431）和一项I期成人试验（NCT 02122913）。主要终点为客观缓解率（ORR）。截至2020年7月20日，已有20例TRK融合阳性肺癌患者接受治疗。研究者评估的15例可评价患者的ORR为73%（95% CI，45 - 92）; 1例（7%）患者完全缓解，10例（67%）患者部分缓解，3例（20%）患者疾病稳定，1例（7%）患者疾病进展为最佳缓解。中位缓解持续时间、无进展生存期和总生存期分别为33.9个月（95% CI，5.6 - 33.9）、35.4个月（95% CI，5.3 - 35.4）和40.7个月（95% CI，17.2至无法估计）。在基线CNS转移的患者中，ORR为63%（95% CI，25 - 91）。不良事件主要为1级或2级。Larotrectinib具有高度活性，在携带NTRK基因融合的晚期肺癌患者（包括CNS转移患者）中具有快速和持久的反应，延长的生存期益处和有利的长期安全性特征。这些发现支持肺癌患者NTRK融合的常规检测。
Larotrectinib is a highly selective and CNS-active tropomyosin receptor kinase (TRK) inhibitor that has demonstrated efficacy across TRK fusion–positive cancers, regardless of the tumor type. The aim of this study was to assess the efficacy and safety of larotrectinib in patients with TRK fusion–positive lung cancers. Data from two global, multicenter, registrational clinical trials of patients treated with larotrectinib were analyzed: a phase II adult and young adult basket trial (NCT02576431) and a phase I adult trial (NCT02122913). The primary end point was objective response rate (ORR). By July 20, 2020, 20 patients with TRK fusion–positive lung cancer had been treated. The ORR by investigator assessment among 15 evaluable patients was 73% (95% CI, 45 to 92); one (7%) patient had a complete response, 10 (67%) had a partial response, three (20%) had stable disease, and one (7%) had progressive disease as best response. The median duration of response, progression-free survival, and overall survival were 33.9 months (95% CI, 5.6 to 33.9), 35.4 months (95% CI, 5.3 to 35.4), and 40.7 months (95% CI, 17.2 to not estimable), respectively. Among patients with baseline CNS metastases, the ORR was 63% (95% CI, 25 to 91). Adverse events were mainly grade 1 or 2. Larotrectinib is highly active with rapid and durable responses, extended survival benefit, and a favorable long-term safety profile in patients with advanced lung cancer harboring NTRK gene fusions, including those with CNS metastases. These findings support routine testing for NTRK fusions in patients with lung cancer.