The Legacy Heritage Oncology Center & Dr. Larry Norton Institute, Soroka Medical Center, Ben-Gurion University, Beer Sheva, Israel.
Medical School for International Health, Ben-Gurion University of the Negev, Beer Sheva, Israel.
Oncology. 2022;100(9):467-474. doi: 10.1159/000525188. Epub 2022 Jun 9.
Non-small cell lung cancer (NSCLC) accounts for most lung cancers and is a leading cause of cancer-related deaths in the USA. Alterations in c-MET, a tyrosine kinase receptor, have been involved in many cases of NSCLC progression and metastasis. Crizotinib and other tyrosine kinase inhibitors (TKIs) have been used in NSCLC treatment with limited success. In this retrospective observational study, we analyzed data from patients diagnosed with lung cancer at Soroka University Medical Center between January 2015 and January 2020. We investigated patient characteristics, including disease-associated mutation type and median survival in response to different TKI treatments. A total of 780 patients with lung cancer were included in the study, 134 of whom had small cell lung cancer and 646 had NSCLC. Of the NSCLC patients, 403 were diagnosed with advanced or metastatic disease, and 374 underwent molecular testing. We identified 16 patients with either c-MET mutations or amplifications who were treated with crizotinib. Of these patients, 7 expressed a c-MET exon 14 skipping mutation while the remaining 9 patients expressed c-MET amplification. Among the patients with a c-MET exon 14 skip mutation, the overall survival was 22.8 months and the median progression-free survival (PFS) on crizotinib treatment was 12.4 months. Of the patients with c-MET amplification, the median overall survival was 5.4 months and the median PFS with crizotinib treatment was 2.6 months. We analyzed the data of a series of cases describing patients diagnosed with different stages of NSCLC, having either a c-MET exon 14 skipping mutation or an amplification mutation, and treated with various TKIs, including crizotinib. We investigated the characteristics of these patient groups in accordance with mutation types and compared median survival between patient groups. Crizotinib was found to be an optimal treatment for NSCLC harboring c-MET exon 14 skipping mutations.
非小细胞肺癌（NSCLC）占大多数肺癌，并是导致美国癌症相关死亡的主要原因。酪氨酸激酶受体 c-MET 的改变与许多 NSCLC 进展和转移有关。克唑替尼和其他酪氨酸激酶抑制剂（TKI）已用于 NSCLC 治疗，但效果有限。在这项回顾性观察研究中，我们分析了 2015 年 1 月至 2020 年 1 月期间在索罗卡大学医学中心诊断为肺癌的患者的数据。我们研究了患者的特征，包括疾病相关突变类型和对不同 TKI 治疗的中位生存情况。共有 780 例肺癌患者纳入本研究，其中 134 例为小细胞肺癌，646 例为 NSCLC。在 NSCLC 患者中，403 例诊断为晚期或转移性疾病，374 例接受了分子检测。我们确定了 16 例接受克唑替尼治疗的 c-MET 突变或扩增患者。这些患者中，7 例存在 c-MET 外显子 14 跳跃突变，其余 9 例存在 c-MET 扩增。在外显子 14 跳跃突变的患者中，总生存期为 22.8 个月，克唑替尼治疗的中位无进展生存期（PFS）为 12.4 个月。在 c-MET 扩增的患者中，中位总生存期为 5.4 个月，克唑替尼治疗的中位 PFS 为 2.6 个月。我们分析了一系列病例的数据，这些病例描述了患有不同阶段 NSCLC 的患者，存在 c-MET 外显子 14 跳跃突变或扩增突变，并接受了各种 TKI 的治疗，包括克唑替尼。我们根据突变类型分析了这些患者群体的特征，并比较了患者群体之间的中位生存期。克唑替尼是治疗携带 c-MET 外显子 14 跳跃突变的 NSCLC 的最佳选择。
