Clinical Experience With Crizotinib in Patients With Advanced ALK-Rearranged Non-Small-Cell Lung Cancer and Brain Metastases
Clinical Experience With Crizotinib in Patients With Advanced ALK-Rearranged Non-Small-Cell Lung Cancer and Brain Metastases
复制标题
DOI：
10.1200/jco.2014.59.0539
复制
发表时间：
2015-06-10
影响因子：
45.3
通讯作者：
Crino, Lucio
中科院分区：
文献类型：
--
作者：
Costa, Daniel B.;Shaw, Alice T.;Crino, Lucio
目的克唑替尼是一种口服激酶抑制剂，已被批准用于治疗ALK重排的非小细胞肺癌（NSCLC）。crizotinib在脑转移瘤患者的临床获益尚未被先前studyed.Patients和MethodsPatients与晚期ALK重排的非小细胞肺癌入组临床试验PROFILE 1005或1007（随机分配到crizotinib）被列入本回顾性分析。允许无症状脑转移（非靶病灶或靶病灶）患者入组。使用RECIST（1.1版）每6周进行一次肿瘤评估。ResultsAt baseline，31%的患者（888例中有275例）有无症状脑转移; 109例未接受过既往治疗，166例接受过既往脑放射治疗。在既往未经治疗的无症状脑转移患者中，12周时的全身疾病控制率（DCR）为63%（95% CI，54%-72%），颅内DCR为56%（95% CI，46%-66%），中位颅内疾病进展时间（TTP）为7个月（95% CI，6.7 - 16.4）。在既往接受过治疗的脑转移患者中，全身DCR为65%（95% CI，57%-72%），颅内DCR为62%（95% CI，54%-70%），中位颅内TTP为13.2个月（95% CI，9.9至未达到）。全身疾病控制的患者在12周时也可能经历颅内疾病控制（相关系数，0.7652; P < .001）。在没有基线脑转移的患者谁开发的疾病进展（n = 253）后开始的crizotinib，20%被诊断为brain metastasis.ConclusionCrizotinib与全身和颅内疾病控制ALK重排的NSCLC患者谁是ALK抑制剂初治和脑转移。然而，接受治疗期间既存颅内病变进展或新发颅内病变是克唑替尼获得性耐药的常见表现。(C)2015年美国临床肿瘤学会
PurposeCrizotinib is an oral kinase inhibitor approved for the treatment of ALK-rearranged non-small-cell lung cancer (NSCLC). The clinical benefits of crizotinib in patients with brain metastases have not been previously studied.Patients and MethodsPatients with advanced ALK-rearranged NSCLC enrolled onto clinical trial PROFILE 1005 or 1007 (randomly assigned to crizotinib) were included in this retrospective analysis. Patients with asymptomatic brain metastases (nontarget or target lesions) were allowed to enroll. Tumor assessments were evaluated every 6 weeks using RECIST (version 1.1).ResultsAt baseline, 31% of patients (275 of 888) had asymptomatic brain metastases; 109 had received no prior and 166 had received prior brain radiotherapy as treatment. Among patients with previously untreated asymptomatic brain metastases, the systemic disease control rate (DCR) at 12 weeks was 63% (95% CI, 54% to 72%), the intracranial DCR was 56% (95% CI, 46% to 66%), and the median intracranial time to progression (TTP) was 7 months (95% CI, 6.7 to 16.4). Among patients with previously treated brain metastases, the systemic DCR was 65% (95% CI, 57% to 72%), the intracranial DCR was 62% (95% CI, 54% to 70%), and the median intracranial TTP was 13.2 months (95% CI, 9.9 to not reached). Patients with systemic disease control were also likely to experience intracranial disease control at 12 weeks (correlation coefficient, 0.7652; P < .001). Among patients without baseline brain metastases who developed progressive disease (n = 253) after initiation of crizotinib, 20% were diagnosed with brain metastases.ConclusionCrizotinib was associated with systemic and intracranial disease control in patients with ALK-rearranged NSCLC who were ALK inhibitor naive and had brain metastases. However, progression of preexisting or development of new intracranial lesions while receiving therapy was a common manifestation of acquired resistance to crizotinib. (C) 2015 by American Society of Clinical Oncology