Kato Yasuhiro, Yamamoto Gou, Watanabe Yasutaka, Yamane Yuki, Mizutani Hideaki, Kurimoto Futoshi, Seike Masahiro, Gemma Akihiko, Akagi Kiwamu, Sakai Hiroshi
Department of Thoracic Oncology, Saitama Cancer Center, 780, Komuro, Ina, Kitaadachi, Saitama, 362-0806, Japan.
Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan.
Int J Clin Oncol. 2021 Jun;26(6):1065-1072. doi: 10.1007/s10147-021-01893-0. Epub 2021 Mar 3.
MET exon 14 skipping mutation, observed in 3-4% of non-small cell lung cancer (NSCLC), is emerging as a targetable alteration. In recent years, immune checkpoint inhibitors (ICI) have been effective in treating several NSCLCs. Our research aimed to investigate the characteristics of patients with NSCLCs harboring MET exon 14 mutations and their response to ICI in Japan.
Among the 1954 consecutive NSCLCs diagnosed at Saitama Cancer Center between 2010 and 2019, MET exon 14 skipping mutations were detected in 68 (3.5%) NSCLCs. We evaluated their characteristics such as programmed cell death ligand 1 (PD-L1) expression.
Median age of patients with NSCLCs harboring MET exon 14 skipping mutations was 73 years. PD-L1 was highly expressed in 17 (70.8%) of the 24 patients examined. Seven patients received ICI monotherapy, and three out of seven had a remarkable treatment response, resulted in objective response rate (ORR) of 42.9% and progression-free survival of 24.7 months. Three patients with donor splice-site mutations showed a long-term treatment response, despite the fact that two with acceptor splice-site mutations demonstrated no response and experienced early disease progression with ICI monotherapy.
Our results indicated that patients with NSCLCs harboring MET exon 14 mutations presented with a high rate of positive PD-L1 expression. ICI treatment showed a high ORR and long-term efficacy for NSCLCs harboring MET exon 14 mutations. Variants of MET exon 14 splice-site mutations may be associated with ICI response.
MET外显子14跳跃突变在3%-4%的非小细胞肺癌（NSCLC）中被观察到，正成为一种可靶向治疗的改变。近年来，免疫检查点抑制剂（ICI）已有效地治疗了多种NSCLC。我们的研究旨在调查日本携带MET外显子14突变的NSCLC患者的特征及其对ICI的反应。
在2010年至2019年期间于埼玉癌症中心连续诊断的1954例NSCLC中，68例（3.5%）NSCLC检测到MET外显子14跳跃突变。我们评估了它们的特征，如程序性细胞死亡配体1（PD-L1）表达。
携带MET外显子14跳跃突变的NSCLC患者的中位年龄为73岁。在24例接受检查的患者中，17例（70.8%）PD-L1高表达。7例患者接受了ICI单药治疗，其中3例有显著的治疗反应，客观缓解率（ORR）为42.9%，无进展生存期为24.7个月。3例供体剪接位点突变患者显示出长期治疗反应，尽管2例受体剪接位点突变患者对ICI单药治疗无反应且疾病早期进展。
我们的结果表明，携带MET外显子14突变的NSCLC患者PD-L1阳性表达率高。ICI治疗对携带MET外显子14突变的NSCLC显示出高ORR和长期疗效。MET外显子14剪接位点突变的变体可能与ICI反应相关。
