Sarah Cannon Cancer Research Institute/Tennessee Oncology, PLLC, 250 25th Ave N, Nashville, TN, 37203, USA.
Massachusetts General Hospital, 55 Fruit St, Boston, MA, 02114, USA.
Target Oncol. 2020 Feb;15(1):55-65. doi: 10.1007/s11523-020-00702-4.
Lorlatinib is a potent, third-generation ALK/ROS1 tyrosine kinase inhibitor (TKI) designed to penetrate the blood-brain barrier.
We report the cumulative incidence of central nervous system (CNS) and non-CNS progression with lorlatinib in patients with ALK-positive non-small-cell lung cancer (NSCLC) previously treated with ALK TKIs.
In an ongoing phase II study (NCT01970865), 198 patients with ALK-positive NSCLC with ≥ 1 prior ALK TKI were enrolled into expansion cohorts (EXP) based on treatment history. Patients received lorlatinib 100 mg once daily. Patients were analyzed for progressive disease, categorized as CNS or non-CNS progression, by independent central review. Cumulative incidence probabilities were calculated adopting a competing risks approach.
Fifty-nine patients received crizotinib as their only prior ALK TKI (EXP2-3A); cumulative incidence rates (CIRs) of CNS and non-CNS progression were both 22% at 12 months in patients with baseline CNS metastases (n = 37), and CIR of non-CNS progression at 12 months was higher versus that for CNS progression in patients without baseline CNS metastases [43% vs. 9% (n = 22)]. In patients who received ≥ 1 prior second-generation ALK TKI [EXP3B-5 (n = 139)], CIR of non-CNS progression at 12 months was higher versus that for CNS progression in patients both with and without baseline CNS metastases (35% vs. 23% (n = 94) and 55% vs. 12% (n = 45), respectively).
Lorlatinib showed substantial intracranial activity in patients with pretreated ALK-positive NSCLC, with or without baseline CNS metastases, whose disease progressed on crizotinib or second-generation ALK TKIs. CLINICALTRIALS.
NCT01970865.
劳拉替尼是一种有效的第三代 ALK/ROS1 酪氨酸激酶抑制剂（TKI），旨在穿透血脑屏障。
我们报告了先前接受过 ALK TKI 治疗的 ALK 阳性非小细胞肺癌（NSCLC）患者使用劳拉替尼治疗时中枢神经系统（CNS）和非 CNS 进展的累积发生率。
在一项正在进行的 II 期研究（NCT01970865）中，根据治疗史，198 名 ALK 阳性 NSCLC 患者（至少有 1 种既往 ALK TKI）被纳入扩展队列（EXP）。患者接受劳拉替尼 100mg 每日一次。通过独立的中央审查，对疾病进展的患者进行分析，分为 CNS 或非 CNS 进展。采用竞争风险方法计算累积发生率概率。
59 名患者仅接受克唑替尼作为其唯一的既往 ALK TKI（EXP2-3A）；基线时有 CNS 转移的患者（n=37），12 个月时 CNS 和非 CNS 进展的累积发生率（CIR）均为 22%，而基线时无 CNS 转移的患者，非 CNS 进展的 CIR 高于 CNS 进展 [43%比 9%（n=22）]。接受≥1 种既往第二代 ALK TKI 治疗的患者（EXP3B-5，n=139），12 个月时非 CNS 进展的 CIR 高于基线时有和无 CNS 转移的患者（35%比 23%（n=94）和 55%比 12%（n=45））。
劳拉替尼在先前接受过治疗的 ALK 阳性 NSCLC 患者中显示出显著的颅内活性，无论基线时是否有 CNS 转移，其疾病在克唑替尼或第二代 ALK TKI 进展后。临床试验。
NCT01970865。
