在III期CROWN试验中，与克唑替尼相比，洛拉替尼显著改善了晚期ALK阳性非小细胞肺癌(NSCLC)患者的无进展生存期(PFS)，并显示出稳健的颅内活性。本研究报告了基线时有无脑转移患者的事后疗效结果，并提供中枢神经系统不良事件(AEs)发生率和处理的数据。

符合条件的患者随机按1:1分配一线氯拉替尼(100 mg每日一次)或克唑替尼(250 mg每日两次);治疗组之间不允许交叉。肿瘤评估，包括CNS磁共振成像，在筛选时进行，然后每隔8周进行一次。对患者报告的结果进行定期评估。

在基线时有脑转移瘤和无脑转移瘤的患者中，通过盲法独立中心审查得出的PFS(12个月PFS率:78%对22%和78%对45%)与氯拉替尼相比有所改善。在基线时有脑转移(7% vs 72%)和无脑转移(1% vs 18%)的患者中，洛拉替尼与克唑替尼相比，CNS进展的12个月累积发生率较低。总的来说，35%的患者使用氯拉替尼后发生中枢神经系统不良事件，大多数为1级严重程度。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。在分析时，56%的中枢神经系统不良事件已经解决(33%未进行干预；洛拉替尼剂量调整后17%)，38%未解决；大多数不需要干预。洛拉替尼剂量调整对PFS无明显影响。

Abstract

Purpose: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

原文链接

pubmed.ncbi.nlm.nih.gov/35605188/

百度浏览   来源 : 医微客   

版权声明：本网站所有注明来源“医微客”的文字、图片和音视频资料，版权均属于医微客所有，非经授权，任何媒体、网站或个人不得转载，授权转载时须注明来源：”医微客”。本网所有转载文章系出于传递更多信息之目的，且明确注明来源和作者，转载仅作观点分享，版权归原作者所有。不希望被转载的媒体或个人可与我们联系，我们将立即进行删除处理。 本站拥有对此声明的最终解释权。