与表皮生长因子受体酪氨酸激酶抑制剂（EGFR-TKI）继发的 METamp 不同，原发性间充质表皮转化因子扩增（METamp）靶向治疗的临床数据很少。原发性 METamp NSCLC 患者的一线治疗选择仍不清楚，特别是免疫检查点抑制剂 (ICIs) 在这些患者中的疗效存在争议。我们回顾性纳入了至少接受过一种全身抗癌治疗的原发性 METamp 患者2018年6月至2023年6月在浙江省肿瘤医院确诊的患者，分析了这些患者不同治疗模式的疗效。我们还评估了原发性 METamp NSCLC 患者中肿瘤免疫微环境 (TIME) 与程序性死亡 1 (PD-1)/程序性死亡配体 1 (PD-L1) 轴之间的潜在关系。高水平 METamp 定义为基因拷贝数 (GCN) ≥ 10 [1]。临床结果包括客观缓解率（ORR）、疾病控制率（DCR）、中位无进展生存期（mPFS）、中位总生存期（mOS）。我们筛查了 2016 名 NSCLC 患者，检测了 36 名原发性 METamp，结果发现1.79%。在患者中，平均 MET GCN 为 4.6，总体 ORR 为 50.0%，DCR 为 77.8%，mPFS 为 5.8 个月，mOS 为 11.7 个月。我们将患者接受的一线治疗分为：免疫化疗（CI组）、抗血管化疗（CA组）、化疗（C组）和MET-TKIs治疗（TKI组）。 CI组、CA组、C组和TKI组的ORR分别为64.3%、16.7%、33.4%和71.4%。这四组的 DCR 分别为 100%、50%、66.7% 和 71.4%。 CI 组的 mPFS 和 mOS 分别比其他组更长（mPFS：8.63 vs 3.73 vs 3.53 vs 5.50 个月，P = 0.021；mOS：15.10 vs 11.73 vs 9.93 vs 13.93 个月，P = 0.023）。 PD-L1 阳性组的 mPFS 长于 PD-L1 阴性组 (P = 0.046)，并且 PD-L1 阳性是 PFS 的独立预后指标 (P = 0.005)。此外，Foxp3阳性表达者的疾病缓解效果显着低于阴性表达者（ORR：33.3% vs 75.0%，P=0.024）。免疫化疗是除靶向治疗外的一线可选治疗策略。具有原发性 METamp 的 NSCLC 患者。 Foxp3 阴性表达可以更好地预测免疫疗法的近期疗效。版权所有 © 2024。由 Elsevier B.V. 出版。

There are few clinical data on targeted therapy for primary mesenchymal-epidermal transforming factor amplification (METamp), unlike METamp secondary to epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs). First-line treatment options for patients with primary METamp NSCLC remain unclear, and in particular, the efficacy of immune checkpoint inhibitors (ICIs) in these patients is controversial.We retrospectively included primary METamp patients who had received at least one line of systemic anticancer therapy, diagnosed at Zhejiang Cancer Hospital from June 2018 to June 2023, and analyzed the efficacies of different treatment patterns for these patients. We also evaluated the potential relationship between the tumor immune microenvironment (TIME) and the programmed death-1 (PD-1)/programmed death ligand-1 (PD-L1) axis in primary METamp NSCLC patients. High-level METamp was defined as gene copy number (GCN) ≥ 10 [1]. The clinical outcomes included objective response rate (ORR), disease control rate (DCR), median progression-free survival (mPFS), median overall survival (mOS).We screened 2016 NSCLC patients and detected 36 primary METamp, resulting in a prevalence of 1.79 %. Among the patients, the average MET GCN was 4.6, the overall ORR was 50.0 %, DCR was 77.8 %, mPFS was 5.8 months and mOS was 11.7 months. We categorized the first-line treatments that patients received as: immuno-chemotherapy (CI-group), antiangio-chemotherapy (CA-group), chemotherapy (C-group) and MET-TKIs therapy (TKI-group). The ORR of CI-group, CA-group, C-group and TKI-group was 64.3 %, 16.7 %, 33.4 % and 71.4 %, respectively. And the DCR of this four groups was 100 %, 50 %, 66.7 % and 71.4 %, respectively. CI-group achieved longer mPFS and mOS than other groups, respectively (mPFS: 8.63 vs 3.73 vs 3.53 vs 5.50 months, P = 0.021; mOS: 15.10 vs 11.73 vs 9.93 vs 13.93 months, P = 0.023). The mPFS was longer in the PD-L1-positive group than in the PD-L1 negative group (P = 0.046) and PD-L1 positivity was an independent prognostic indicator for PFS (P = 0.005). In addition, the disease remission effect was significantly lower in Foxp3-positive expressors than in negative expressors (ORR: 33.3 % vs 75.0 %, P = 0.024).Immuno-chemotherapy is a first-line optional treatment strategy in addition to targeted therapy for NSCLC patients with primary METamp. Foxp3-negative expression better predicts the near-term efficacy of immunotherapy.Copyright © 2024. Published by Elsevier B.V.