Differential Crizotinib Response Duration Among ALK Fusion Variants in ALK-Positive Non-Small-Cell Lung Cancer
Differential Crizotinib Response Duration Among ALK Fusion Variants in ALK-Positive Non-Small-Cell Lung Cancer
复制标题
DOI：
10.1200/jco.2015.65.8732
复制
发表时间：
2016-10-01
影响因子：
45.3
通讯作者：
Yatabe, Yasushi
中科院分区：
文献类型：
--
作者：
Yoshida, Tatsuya;Oya, Yuko;Yatabe, Yasushi
目的间变性淋巴瘤激酶（ALK）重排阳性的非小细胞肺癌可以用ALK酪氨酸激酶抑制剂（TKI）如克唑替尼有效治疗，但疗效大小和持续时间存在差异。已经确定了几种ALK变体，但很少有研究关注不同ALK变体对克唑替尼疗效的影响。患者和方法在2007年1月至2014年12月期间，55例接受克唑替尼作为初始ALK- tki治疗的患者中，我们发现35例患者的肿瘤标本可以通过逆转录聚合酶链反应来评估ALK变异。我们根据客观缓解率和根据ALK变异的无进展生存期（PFS）回顾性评估了克唑替尼的疗效。结果ALK最常见的变异是1型变异19例（54%），其次是2型变异5例（14%），3a/3b型变异4例（12%），其他变异7例（20%）。所有患者的客观缓解率为69%，而变异1组和非变异1组的客观缓解率分别为74%和63%。变异1患者的中位PFS时间明显长于非变异1患者（中位PFS分别为11.0个月[95% CI， 6.5 ~ 43.0个月]和4.2个月[95% CI， 1.6 ~ 10.2个月]，P < 0.05）。多变量分析确定了与PFS持续时间相关的两个显著因素，ALK变异1（风险比，0.350;95% CI, 0.128 ~ 0.929; P < 0.05）和进展阶段（风险比，4.646;95% CI, 1.381 ~ 21.750, P < 0.05）。结论克唑替尼治疗ALK变异体1的疗效优于非变异体1。ALK变异状态可能影响ALK- tkis的疗效。(C) 2016年由美国临床肿瘤学会出版。
PurposeAnaplastic lymphoma kinase (ALK) rearrangement-positive non-small-cell lung cancers can be effectively treated with an ALK tyrosine kinase inhibitor (TKI) such as crizotinib, but the response magnitude and duration are heterogeneous. Several ALK variants have been identified, but few studies have focused on the effects of different ALK variants on the efficacy of crizotinib.Patients and MethodsAmong 55 patients treated with crizotinib as the initial ALK-TKI between January 2007 and December 2014, we identified 35 patients with tumor specimens that could be evaluated for ALK variants by reverse transcription polymerase chain reaction. We retrospectively evaluated the efficacy of crizotinib on the basis of the objective response rate and progression-free survival (PFS) according to the ALK variants.ResultsThe most frequent ALK variant was variant 1 in 19 patients (54%), followed by variant 2 in five patients (14%), variant 3a/3b in four patients (12%), and other variants in seven patients (20%). Objective response rate was 69% in all patients, whereas it was 74% and 63% in the variant 1 and non-variant 1 groups, respectively. The median PFS time was significantly longer in patients with variant 1 than in those with non-variant 1 (median PFS, 11.0 months [95% CI, 6.5 to 43.0 months] v 4.2 months [95% CI, 1.6 to 10.2 months], respectively; P < .05). Multivariable analysis identified two significant factors associated with PFS duration, ALK variant 1 (hazard ratio, 0.350; 95% CI, 0.128 to 0.929; P < .05) and advanced stage (hazard ratio, 4.646; 95% CI, 1.381 to 21.750; P < .05).ConclusionOur results indicate the better efficacy of crizotinib in patients with ALK variant 1 versus non-variant 1. The ALK variant status might affect the efficacy of ALK-TKIs. (C) 2016 by American Society of Clinical Oncology.