Yang Shuo, Wang Yan, Zhao Chao, Li Xuefei, Liu Qian, Mao Shiqi, Liu Yiwei, Yu Xiaofei, Wang Wanying, Tian Qinrun, Pan Yingying, Xiong Anwen, Chen Bin, Gao Guanghui, Li Wei, He Yayi, Wu Fengying, Chen Xiaoxia, Su Chunxia, Ren Shengxiang, Zhou Caicun
Department of Medical Oncology, Shanghai Pulmonary Hospital and Thoracic Cancer Institute, Tongji University School of Medicine, Shanghai, China.
Department of Lung Cancer and Immunology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China.
Transl Lung Cancer Res. 2021 Feb;10(2):753-765. doi: 10.21037/tlcr-20-559.
Chemotherapy remains the standard care for mutated advanced non-small cell lung cancer (NSCLC) even though several targeted drugs showed promising results in preliminary stages. This study aimed to investigate the association of mutation variants with clinical features and the efficacy of chemotherapy in patients with mutated advanced NSCLC.
ARMS-PCR was used to identify HER2 mutation in patients without common oncogenic alterations. Patients with detailed information were further enrolled for analysis of clinical features and efficacy of first line chemotherapy. Survival data was analyzed by Kaplan-Meier method and compared by log-rank test. Brain metastasis incidence was analyzed and compared by Gray's test.
YVMA insertion accounted for the majority (68.4%, 67/98) of HER2 mutation, and associated with significantly higher incidence of baseline extrathoracic metastasis (P=0.009), notably brain metastasis (P=0.004). Among 82 patients those received first line chemotherapy, YVMA insertion remarkably associated with inferior treatment outcomes, namely, a significantly shorter median progression free survival (PFS) and lower objective response rate (ORR) both in total patients (PFS: 5.2 7.7 m, P=0.038; ORR: 30.9% 51.9%, P=0.09) and pemetrexed subgroup (PFS: 5.2 6.5 m, P=0.022; ORR: 31.8% 60.0%, P=0.054). Multivariate analysis further established YVMA insertion as prognostic factor of worse PFS both for total patients (HR =1.578, 95% CI, 0.956-2.606) and patients received pemetrexed-based chemotherapy (HR =1.789, 95% CI, 1.013-3.160). In addition, YVMA insertion associated with higher incidence of lifetime brain metastasis (P=0.002) compared by Gray's test, with estimated 12-month brain metastasis incidence as 40.2% compared with 3.6% in the non-YVMA group.
YVMA insertion is associated with a higher incidence of brain metastasis, and inferior outcomes to chemotherapy than non-YVMA variants in patients with advanced NSCLC and HER2 kinase domain mutations, which emphasized the unmet need of more potent anti-cancer therapies with high blood-brain barrier (BBB) penetration capacity for patients with YVMA insertion.
尽管几种靶向药物在初步阶段显示出有前景的结果，但化疗仍然是突变型晚期非小细胞肺癌（NSCLC）的标准治疗方法。本研究旨在调查突变变体与临床特征的关联以及化疗对突变型晚期NSCLC患者的疗效。
采用ARMS-PCR法在无常见致癌改变的患者中鉴定HER2突变。纳入有详细信息的患者，进一步分析一线化疗的临床特征和疗效。生存数据采用Kaplan-Meier法分析，并通过对数秩检验进行比较。脑转移发生率采用Gray检验进行分析和比较。
YVMA插入占HER2突变的大多数（68.4%，67/98），且与基线胸外转移发生率显著较高相关（P = 0.009），尤其是脑转移（P = 0.004）。在82例接受一线化疗的患者中，YVMA插入与较差的治疗结果显著相关，即在所有患者中，无进展生存期（PFS）中位数显著缩短（PFS：5.2对7.7个月，P = 0.038），客观缓解率（ORR）较低（ORR：30.9%对51.9%，P = 0.09），在培美曲塞亚组中也是如此（PFS：5.2对6.5个月，P = 0.
