Comparable clinical outcomes in patients with HER2-mutant and EGFR-mutant lung adenocarcinomas
Comparable clinical outcomes in patients with HER2-mutant and EGFR-mutant lung adenocarcinomas
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DOI：
10.1002/gcc.22442
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发表时间：
2017-05-01
影响因子：
3.7
通讯作者：
Shih, Jin-Yuan
中科院分区：
文献类型：
--
作者：
Gow, Chien-Hung;Chang, Hou-Tai;Shih, Jin-Yuan
HER 2是肺癌的主要增殖驱动因素。HER 2基因异常影响肺腺癌（ADC）的预后。使用888例亚洲肺癌患者的RNA样本进行一步逆转录聚合酶链反应，以检测HER 2、EGFR、KRAS、ALK和ROS 1突变。分析HER 2突变阳性肺ADC患者的人口统计学数据和治疗结局，并与HER 2突变阴性肿瘤患者进行比较。在40例（4.5%）肺ADC患者中发现了HER 2突变。HER 2突变倾向于发生在晚期疾病和从不吸烟的男性患者中。A775_G776insYVMA（n=22，55%）是最常见的HER 2突变，其次是P780_Y781insGSP（n=4，10%）。对于诊断为IIIB/IV期疾病的患者，HER 2突变患者的临床结局与EGFR突变患者相当（P=0.721，对数秩检验），与研究基因中缺乏驱动突变的患者相比，总生存期（OS）更好（P=0.033，Breslow检验）。具体而言，接受化疗或靶向药物治疗（即使未接受阿法替尼或抗HER 2靶向治疗）的IV期HER 2突变型肿瘤肺ADC患者的临床结局与携带EGFR外显子19缺失或L 858 R突变的肺ADC患者相似（P=0.870）。此外，多变量分析表明，HER 2突变状态不是IV期肺癌OS降低的主要风险因素。总之，携带HER 2突变的肺ADC显示出与其他驱动突变不同的特征，包括晚期疾病的化疗敏感性增加。
HER2 is a major proliferative driver in lung cancer. HER2 gene aberrations impact the prognosis of lung adenocarcinoma (ADC). A one-step reverse transcription-polymerase chain reaction was performed using RNA samples from 888 Asian lung cancer patients to detect HER2, EGFR, KRAS, ALK, and ROS1 mutations. The demographic data and treatment outcomes of HER2 mutation-positive lung ADC patients were analyzed and compared to those with HER2 mutation-negative tumors. HER2 mutation was identified in 40 (4.5%) lung ADC patients. HER2 mutations tended to occur in male patients with advanced-stage disease and never-smokers. A775_G776insYVMA (n=22, 55%) was the most prevalent HER2 mutation, followed by P780_Y781insGSP (n=4, 10%). For patients diagnosed with stage-IIIB/IV disease, HER2-mutant patients showed clinical outcomes comparable to EGFR-mutant patients (P=0.721, log-rank test) and a better overall survival (OS) compared to patients lacking driver mutations in the investigated genes (P=0.033, Breslow test). Specifically, lung ADC patients with stage-IV HER2-mutant tumors treated with chemotherapy or targeted agents, even without afatinib or anti-HER2 targeted therapy, showed similar clinical outcomes to lung ADC patients harboring EGFR exon 19 deletion or L858R mutations (P=0.870). In addition, multivariate analysis indicated that HER2 mutation status was not a major risk factor for diminished OS in stage-IV lung cancer. In conclusion, lung ADC harboring HER2 mutations showed distinct characteristics from other driver mutations, including increased chemosensitivity with in advanced stage disease.