Lorlatinib对ALK阳性晚期非小细胞肺癌患者颅内疗效

SCI

8 June 2022

Post Hoc Analysis of Lorlatinib Intracranial Efficacy and Safety in Patients With ALK-Positive Advanced Non–Small-Cell Lung Cancer From the Phase III CROWN Study

 (JCO, 44.544)

• Solomon Benjamin J,Bauer Todd M,Ignatius Ou Sai-Hong et al. ALKPost Hoc Analysis of Lorlatinib Intracranial Efficacy and Safety in Patients With -Positive Advanced Non-Small-Cell Lung Cancer From the Phase III CROWN Study.[J] .J Clin Oncol, 2022, undefined: JCO2102278.

Purpose 目的

Lorlatinib significantly improved progression-free survival (PFS) versus crizotinib and showed robust intracranial activity in patients with previously untreated advanced ALK-positive non-small-cell lung cancer (NSCLC) in the phase III CROWN trial. Here, we report post hoc efficacy outcomes in patients with and without brain metastases at baseline, and present data on the incidence and management of CNS adverse events (AEs) in CROWN.

在III期CROWN试验中，与克唑替尼相比，Lorlatinib显著提高了无进展生存期(PFS)，并在先前未经治疗的晚期ALK阳性非小细胞肺癌(NSCLC)患者中显示了强大的颅内活性。在本研究中，我们报告了基线时有或没有脑转移的患者的事后疗效结果，并提供了冠状动脉病变中中枢神经系统不良事件(AEs)的发生率和处理的数据。

  Methods 方法

Eligible patients were randomly assigned 1:1 to first-line lorlatinib (100 mg once daily) or crizotinib (250 mg twice a day); no crossover between treatment arms was permitted. Tumor assessments, including CNS magnetic resonance imaging, were performed at screening and then at 8-week intervals. Regular assessments of patient-reported outcomes were conducted.

符合条件的患者随机按1:1分配一线Lorlatinib(100 mg, 1次/ d)或克唑替尼(250 mg, 2次/ d);治疗手段之间不允许交叉。肿瘤评估，包括中枢神经系统磁共振成像，在筛查时进行，然后每隔8周进行一次。定期评估患者报告的结果。

Results 结果

PFS by blinded independent central review was improved with lorlatinib versus crizotinib in patients with and without brain metastases at baseline (12-month PFS rates: 78% v 22% and 78% v 45%, respectively). Lorlatinib was associated with lower 12-month cumulative incidence of CNS progression versus crizotinib in patients with (7% v 72%) and without (1% v 18%) brain metastases at baseline. In total, 35% of patients had CNS AEs with lorlatinib, most of grade 1 severity. Occurrence of CNS AEs did not result in a clinically meaningful difference in patient-reported quality of life. At analysis, 56% of CNS AEs had resolved (33% without intervention; 17% with lorlatinib dose modification), and 38% were unresolved; most required no intervention. Lorlatinib dose modification did not notably influence PFS.

基线时，经盲法独立中心评价，与克唑替尼相比，Lorlatinib对脑转移和无脑转移患者的PFS有所改善(12个月的PFS率分别为78% vs 22%和78% vs 45%)。与克唑替尼相比，在基线有(7% v 72%)和无(1% v 18%)脑转移的患者中，Lorlatinib与CNS进展的12个月累积发生率较低相关。总的来说，35%的患者在使用Lorlatinib时有中枢神经系统AEs，大多数为1级严重。CNS AEs的发生并没有导致患者报告的生活质量有临床意义的差异。分析时，56%的CNS AEs已溶解(33%未进行干预;17%接受Lorlatinib剂量调整)，38%未得到解决;大多数不需要干预。Lorlatinib剂量调整对PFS无显著影响。

Conclusions 结论

First-line lorlatinib improved PFS outcomes and reduced CNS progression versus crizotinib in patients with advanced ALK-positive non-small-cell lung cancer with or without brain metastases at baseline. Half of all CNS AEs resolved without intervention or with lorlatinib dose modification.

基线时，与克唑替尼相比，一线Lorlatinib改善ALK阳性晚期非小细胞肺癌伴或不伴脑转移患者的PFS结果和减少CNS进展。半数的CNS AEs在不干预或调整剂量的情况下得到了解决。

打赏