据报道，所有非小细胞肺癌 (NSCLC) 病例中 2%-5% 发生 HER2 突变。使用免疫检查点抑制剂（ICIs）加铂类化疗作为一线治疗的 HER2 突变 NSCLC 患者的临床结果仍不清楚。使用 LC-SCRUM-Asia 的大型临床基因组数据库，临床结果仍不清楚。研究人员对 HER2 突变 NSCLC 患者的基因组特征和治疗结果进行了调查。在 LC-SCRUM-Asia 数据库登记的 15,251 名 NSCLC 患者中，有 402 名患者 (2.6%) 检测到肿瘤 HER2 突变。 HER2 突变最常见的亚型是外显子 20 框内插入 (79%)，其次是除 Exon20ins 之外的酪氨酸激酶结构域突变 (10%) 和胞外结构域突变 (7%)。与携带 EGFR 突变或 ALK 融合的 NSCLC 相比，携带 HER2 突变的 NSCLC 显示出更高的肿瘤突变负荷 (TMB)（中位值：每兆碱基分别为 4.22 个突变、2.54 个突变和 2.52 个突变）。在 402 名患者中，268 名患者接受了含 ICI 的铂类化疗（Chemo-ICI，n = 95）或无 ICI（单独化疗，n = 173）作为一线治疗。与单独化疗组相比，化疗 ICI 组的无进展生存期 (PFS) 显着更长（中位时间 8.5 个月与 6.3 个月；HR [95%CI]：0.66 [0.50-0.88]；P < 0.005 ）。多变量分析发现，除铂类化疗外，使用 ICI 是 PFS 的独立有利预后因素。 Chemo-ICI 组和单纯化疗组患者的总生存期没有显着差异（中位时间 31.1 个月与 23.3 个月；HR [95%CI]：0.80 [0.57-1.12]，P = 0.20）。在一线治疗中将 ICI 加入铂类化疗可能会改善 HER2 突变 NSCLC 患者的 PFS。相对较高的 TMB 可能与接受 ICI 铂类化疗的 HER2 突变 NSCLC 患者的 PFS 延长有关。版权所有 © 2024 Elsevier B.V. 保留所有权利。

HER2 mutations are reported to occur in 2%-5% of all cases of non-small cell lung cancer (NSCLC). The clinical outcomes in patients with HER2-mutant NSCLC treated with immune checkpoint inhibitors (ICIs) plus platinum-based chemotherapy as 1st line treatment still remain unclear.Using the large-scale clinico-genomic database of LC-SCRUM-Asia, the clinico-genomic characteristics and therapeutic outcomes of patients with HER2-mutant NSCLC were investigated.Of the 15,251 patients with NSCLC enrolled in the LC-SCRUM-Asia database, tumor HER2 mutations were detected in 402 patients (2.6 %). The most common subtype of HER2 mutations was exon 20 in-frame insertions (79 %), followed in frequency by mutations in the tyrosine kinase domain other than Exon20ins (10 %) and mutations in extracellular domains (7 %). NSCLCs harboring HER2 mutations showed a higher tumor mutation burden (TMB) as compared with NSCLCs harboring EGFR mutations or ALK fusions (median: 4.22 vs. 2.54 and 2.52 mutation per megabase, respectively). Of the 402 patients, 268 patients had received platinum-based chemotherapy with ICIs (Chemo-ICI, n = 95) or without ICI (Chemo-alone, n = 173) as 1st line treatment. The progression-free survival (PFS) was significantly longer in the Chemo-ICI group as compared with the Chemo-alone group (median 8.5 vs. 6.3 months; HR [95 %CI]: 0.66 [0.50-0.88]; P < 0.005). Multivariate analysis identified use of ICIs in addition to platinum-based chemotherapy as an independent favorable prognostic factor for PFS. There was no significant difference in the overall survival between the patients of the Chemo-ICI and Chemo-alone groups (median 31.1 vs. 23.3 months; HR [95 %CI]: 0.80 [0.57-1.12], P = 0.20).Addition of ICIs to platinum-based chemotherapy in 1st line treatment may improve the PFS in patients with HER2-mutant NSCLC. The relatively high TMB might be involved in the prolongation of the PFS in patients with HER2-mutant NSCLC receiving platinum-based chemotherapy with ICIs.Copyright © 2024 Elsevier B.V. All rights reserved.