Background: Human epidermal growth factor receptor 2 (HER2) is one of the driver genes of non-small cell lung cancer (NSCLC). Several studies have shown that the efficacy of pemetrexed in HER2-mutant NSCLC is controversial. The aim of this study is to investigate the efficacy of pemetrexed combined with platinum chemotherapy in patients with HER2-mutant and HER2 wild-type lung adenocarcinoma.
Methods: The clinical data of 106 cases of EGFR, ALK, ROS-1, KRAS, BRAF, RET and MET-negative patients with advanced lung adenocarcinoma patients who diagnosed by histopathology in the First Affiliated Hospital of Zhengzhou University were retrospectively reviewed. The relationships between HER2 gene status, clinical characteristics and response and progression-free survival (PFS) were analyzed.
Results: All of the 106 patients' HER2 status were determined. HER2 mutations occurred in 32 cases (30.2%), no mutations in 74 cases (69.8%). HER2 mutations were common in young, non-smoking and female patients. All patients received first-line pemetrexed and platinum-based chemotherapy. The objective response rate (ORR) and disease control rate (DCR) of patients with HER2-mutant lung adenocarcinoma were significantly higher than those without HER2 mutations (40.6% vs 14.9%, χ²=8.464, P=0.004; 93.8% vs 68.9%, χ²=6.327, P=0.012), and the difference was statistically significant. According to univariate analysis, the PFS was significantly associated with the brain metastases, maintenance chemotherapy and HER2 gene status (P<0.05), but not with age, gender, smoking history, oligometastases, liver metastases and type of platinum (P>0.05). Cox multivariate analysis indicated that HER2 mutation was an independent positive prognostic factor of PFS (P=0.038).
Conclusions: HER2-mutant lung adenocarcinoma patients with first-line pemetrexed combined with platinum chemotherapy have greater clinical benefit than HER2 wild-type patients.
【中文题目：HER2基因状态与晚期肺腺癌患者一线 培美曲塞联合铂类化疗疗效的关系】 【中文摘要：背景与目的 人类表皮生长因子受体2（human epidermal growth factor receptor 2, HER2）突变是非小细胞肺癌（non-small cell lung cancer, NSCLC）的分子标记物之一，研究显示培美曲塞在HER2突变NSCLC中的疗效存在争议。本研究拟探讨培美曲塞联合铂类化疗在HER2突变和HER2野生型肺腺癌患者中的疗效。方法 回顾性分析在郑州大学第一附属医院经组织病理学证实的106例EGFR、ALK、ROS-1、KRAS、BRAF、RET、MET均为阴性的晚期肺腺癌患者的临床资料。分析HER2基因状态、临床特征、化疗疗效及无进展生存期（progression-free survival, PFS）之间的关系。结果 106例患者均进行了HER2基因检测，HER2突变32例（30.2%），未发生突变74例（69.8%）。HER2突变在年轻、未吸烟、女性患者中多见。所有患者均接受一线培美曲塞联合铂类的化疗，HER2突变肺腺癌患者的客观缓解率（objective response rate, ORR）和疾病控制率（disease control rate, DCR）均高于HER2野生型患者（40.6% vs 14.9%, χ²=8.464, P=0.004; 93.8% vs 68.9%, χ²=6.327, P=0.012），差异有统计学意义。单因素分析显示：PFS与有无脑转移、有无维持化疗和HER2基因状态相关（P<0.05），而与年龄、性别、是否有吸烟史、是否寡转移、有无肝转移及铂的种类无关（P>0.05）。Cox多因素分析显示：HER2突变是PFS的独立正性预后因素（P=0.038）。结论 HER2突变相比HER2野生型肺腺癌患者一线应用培美曲塞联合铂类的化疗有更大的临床获益。 】 【中文关键词：肺肿瘤；HER2；培美曲塞；一线化疗】.
Keywords: First-line chemotherapy; HER2; Lung neoplasms; Pemetrexed.