Karmanos Cancer Institute/Wayne State University, Detroit, MI; St Marianna University School of Medicine, Kawasaki, Japan.
Karmanos Cancer Institute/Wayne State University, Detroit, MI.
Clin Lung Cancer. 2022 Jan;23(1):52-59. doi: 10.1016/j.cllc.2021.08.012. Epub 2021 Oct 18.
HER2 alteration (mutation and/or amplification) is associated with poor survival in NSCLC and can mediate resistance to EGFR tyrosine kinase inhibitors.
We retrospectively analyzed de-identified molecular information from 12,946 NSCLC samples that underwent next-generation sequencing (NGS) with Caris Life Sciences. The objectives were to determine the prevalence and type of HER2 alterations with and without EGFR as a co-mutation. Insurance claims were utilized to obtain outcomes data.
Three hundred and twenty-one patients (2.5%) had HER2 alteration: mutation in 197 patients and amplification in 134. Median age was 65 years and 62% were female. A total of 84% were adenocarcinoma. HER2 exon 20 insertion was most common (69%). A total of 1551 (12%) patients had EGFR mutations. Among samples with EGFR mutations, 24 (1.5%) had concurrent HER2 alteration (8 with HER2 mutation and 16 with amplification). Among 8 patients who had both EGFR and HER2 mutations, 3 had EGFR exon 19 deletions and exon 8 HER2 mutation (S310F). One-third of the patients (7/21) with HER2 extracellular domain (ECD) mutation had co-occurring EGFR mutations. All 7 were S310. Patients with concurrent EGFR mutation and HER2 amplification had longer median time on treatment with EGFR TKI(s) than those with EGFR mutation without HER2 amplification (HR 2.284, P =.004).
A minority of NSCLC samples with EGFR mutations had HER2 alterations. In patients with both mutations, exon 21 mutations for EGFR and exon 8 mutations for HER2 were common. It will be critical to continue to accumulate valuable clinical data for further real-world outcomes analysis.
HER2 改变（突变和/或扩增）与 NSCLC 的不良预后相关，并可介导对 EGFR 酪氨酸激酶抑制剂的耐药性。
我们回顾性分析了 Caris Life Sciences 公司进行下一代测序（NGS）的 12946 例 NSCLC 样本的去识别分子信息。目的是确定 HER2 改变的流行率和类型，以及有无 EGFR 共突变。利用保险索赔获得结果数据。
321 例患者（2.5%）存在 HER2 改变：197 例为突变，134 例为扩增。中位年龄为 65 岁，62%为女性。共有 84%为腺癌。HER2 外显子 20 插入最为常见（69%）。共有 1551 例（12%）患者存在 EGFR 突变。在存在 EGFR 突变的样本中，24 例（1.5%）存在 HER2 改变（8 例为 HER2 突变，16 例为扩增）。在 8 例同时存在 EGFR 和 HER2 突变的患者中，有 3 例为 EGFR 外显子 19 缺失和外显子 8 HER2 突变（S310F）。三分之一（7/21）的 HER2 细胞外结构域（ECD）突变患者存在共发生的 EGFR 突变。所有 7 例均为 S310。存在同时 EGFR 突变和 HER2 扩增的患者接受 EGFR TKI（s）治疗的中位时间长于 EGFR 突变而无 HER2 扩增的患者（HR 2.284，P =.004）。
少数 EGFR 突变的 NSCLC 样本存在 HER2 改变。在同时存在这两种突变的患者中，EGFR 的外显子 21 突变和 HER2 的外显子 8 突变较为常见。为了进一步进行真实世界结局分析，继续积累有价值的临床数据至关重要。
