Wang Wen-Xian, Xu Chun-Wei, Chen Yan-Ping, Liu Wei, Zhong Li-Hua, Chen Fang-Fang, Zhuang Wu, Huang Yun-Jian, Huang Zhang-Zhou, Chen Rong-Rong, Guan Yan-Fang, Yi Xin, Lv Tang-Feng, Zhu Wei-Feng, Lu Jian-Ping, Wang Xiao-Jiang, Shi Yi, Lin Xian-Dong, Chen Gang, Song Yong
Department of Chemotherapy, Zhejiang Cancer Hospital, Hangzhou 310022, China.
Department of Pathology, Fujian Provincial Cancer Hospital, Fujian Medical University Cancer Hospital, Fuzhou 350014, China.
J Thorac Dis. 2018 May;10(5):2991-2998. doi: 10.21037/jtd.2018.04.98.
Advanced non-small cell lung cancer (NSCLC) patients who harbor anaplastic lymphoma kinase () rearrangement are sensitive to an ALK inhibitor (crizotinib), but not all -positive patients benefit equally from crizotinib treatment. We analyze the impact of mutations on response to crizotinib in patients with rearrangement NSCLC.
Sixty-six rearrangement NSCLC patients receiving crizotinib were analyzed. 21 cases were detected successfully by the next generation sequencing validation FFPE before crizotinib. mutations were evaluated in 8 patients in relation to disease control rate (DCR), objective response rate (ORR), progression-free survival (PFS) and overall survival (OS).
mutations were observed in 2 (25.00%), 1 (12.50%), 1 (12.50%) and 4 (50.00%) patients in exons 5, 6, 7 and 8, respectively. The majority of patients were male (75.00%, 6/8), less than 65 years old (62.50%, 5/8) and never smokers (75.00%, 6/8). ORR and DCR for crizotinib in the entire case series were 61.90% and 71.43%, respectively. Statistically significant difference was observed in terms of PFS and OS between gene wild group and mutation group patients (P=0.038, P=0.021, respectively).
mutations reduce responsiveness to crizotinib and worsen prognosis in rearrangement NSCLC patients.
携带间变性淋巴瘤激酶（ALK）重排的晚期非小细胞肺癌（NSCLC）患者对ALK抑制剂（克唑替尼）敏感，但并非所有ALK阳性患者都能从克唑替尼治疗中同等获益。我们分析了ALK突变对ALK重排NSCLC患者克唑替尼反应的影响。
分析66例接受克唑替尼治疗的ALK重排NSCLC患者。21例在克唑替尼治疗前通过二代测序验证FFPE成功检测到。对8例患者的ALK突变进行疾病控制率（DCR）、客观缓解率（ORR）、无进展生存期（PFS）和总生存期（OS）评估。
分别在5、6、7和8外显子中观察到2例（25.00%）、1例（12.50%）、1例（12.50%）和4例（50.00%）患者发生ALK突变。大多数患者为男性（75.00%，6/8），年龄小于65岁（62.50%，5/8）且从不吸烟（75.00%，6/8）。整个病例系列中克唑替尼的ORR和DCR分别为61.90%和71.43%。ALK基因野生型组和突变组患者在PFS和OS方面观察到统计学显著差异（分别为P = 0.038，P = 0.021）。
ALK突变降低了ALK重排NSCLC患者对克唑替尼的反应性并恶化预后。
