Department of Medical Oncology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Tongji University Medical School Cancer Institute, No. 507 Zheng Min Road, Shanghai, 200433, People's Republic of China.
Department of Respiratory Medicine, Huaihe Hospital, Henan University, Kaifeng, People's Republic of China.
BMC Cancer. 2018 Mar 27;18(1):326. doi: 10.1186/s12885-018-4277-x.
HER2 mutation has been found to be an oncogenic driver gene in non-small cell lung cancers(NSCLC) and HER2-directed therapies have shown promising results in this unique population, while little is known about its association with outcomes of chemotherapy. The aim of this study was to investigate the efficacy of first line chemotherapy in patients with advanced HER2-mutant lung adenocarcinomas.
Patients with advanced NSCLC(N = 1714) initially underwent testing for EGFR, KRAS, BRAF mutations and ALK, ROS1 rearrangements, and negative cases were then assessed for HER2 mutations using the method of amplification refractory mutation system(ARMS). The efficacy of first line pemetrexed-based chemotherapy was investigated in patients with HER2-mutant and those with EGFR-mutant, ALK/ROS1-rearranged and KRAS-mutant advanced adenocarcinomas.
HER2 mutations were detected in 29 of 572(5.1%) specimens from a selected population of EGFR/KRAS/BRAF/ALK/ROS1 negative patients. All of them are adenocarcinomas. Among patients with HER2-mutant lung cancers, 25 received pemetrexed-based first line chemotherapy. The objective response rate(ORR) was 36.0%. Their median progression free survival(PFS) was 5.1 months, which was similar with that of KRAS-mutant group (n = 40,5.0 months, p = 0.971), numerically shorter than that of EGFR-mutant group(n = 74, 6.5 months, p = 0.247) and statistically significantly shorter than that of ALK/ROS1-rearranged group (n = 39,9.2 months, p = 0.004). Furthermore, HER2 variants subgroup analysis showed that PFS was inferior in A775_G776insYVMA group compared with other variants (4.2 vs 7.2 months, p = 0.085).
Patients with advanced HER2-mutant lung adenocarcinomas showed an inferior outcome of first line pemetrexed-based chemotherapy compared to those with ALK/ROS1 rearrangements, which strengthen the need for effective HER2-targeted drugs in clinical practice.
HER2 突变已被发现是非小细胞肺癌（NSCLC）的致癌驱动基因，HER2 靶向治疗在这一独特人群中显示出了良好的效果，而关于其与化疗结果的关系知之甚少。本研究旨在探讨一线化疗在晚期 HER2 突变型肺腺癌患者中的疗效。
对 1714 例晚期 NSCLC 患者进行 EGFR、KRAS、BRAF 突变和 ALK、ROS1 重排检测，阴性病例采用扩增受阻突变系统（ARMS）检测 HER2 突变。分析 HER2 突变与 EGFR 突变、ALK/ROS1 重排、KRAS 突变的晚期腺癌患者接受培美曲塞为基础的一线化疗的疗效。
在选择的 EGFR/KRAS/BRAF/ALK/ROS1 阴性患者中，572 例标本中有 29 例（5.1%）检测到 HER2 突变。所有病例均为腺癌。在 HER2 突变型肺癌患者中，25 例接受培美曲塞为基础的一线化疗。客观缓解率（ORR）为 36.0%。中位无进展生存期（PFS）为 5.1 个月，与 KRAS 突变组（n=40，5.0 个月，p=0.971）相似，略短于 EGFR 突变组（n=74，6.5 个月，p=0.247），与 ALK/ROS1 重排组（n=39，9.2 个月，p=0.004）相比具有统计学意义。此外，HER2 变异亚组分析显示，A775_G776insYVMA 变异组的 PFS 劣于其他变异组（4.2 与 7.2 个月，p=0.085）。
与 ALK/ROS1 重排相比，晚期 HER2 突变型肺腺癌患者一线培美曲塞为基础化疗的疗效较差，这加强了在临床实践中使用有效的 HER2 靶向药物的必要性。
