比较 osi 与早期一代 TKI 对于具有非典型 EGFR 突变 (AM)（例如 L861Q、G719X、S768I 和外显子 20）的 mNSCLC 的疗效的数据有限。我们对 2007 年以来接受治疗的 EGFR 突变 mNSCLC 患者进行了单机构回顾性分析到 2023 年，使用 1L TKI，比较接受 OSI、阿法替尼和厄洛替尼治疗的 AM 患者的结果。从电子病历中提取基线人口统计数据、疾病特征、治疗史、毒性和临床结果，并使用独立样本 t 检验和卡方分析对 TKI 进行比较。通过 Kaplan-Meier 对数秩分析和 Cox 多变量回归比较中位无进展生存期 (mPFS) 和总生存期 (mOS)。 在 355 名 EGFR 突变 mNSCLC 患者中，36 名 (10%) 携带 G719X 中的 AM（N=21） ; 6 %)、外显子 20 (N=11; 3 %)、L861Q (N=7; 2 %)、S768I (N=4; 1 %)、C797S (N=1; 0.3 %); 6名患者存在复合突变。具有经典突变 (CM) 的患者与具有 AM 的患者具有相似的基线人口统计学和疾病特征以及 TKI 的使用情况 (p = 0.124)。在 AM 患者中，osi 的 mPFS (22 m) 优于阿法替尼 (12 m；p = 0.005) 或厄洛替尼 (9 m；p = 0.001)。同样，osi (32 m) 的 mOS 优于阿法替尼 (21 m；p = 0.032) 或厄洛替尼 (17 m；p = 0.011)。因 AE 导致的剂量减少率，osi (19%) 低于阿法替尼 (24%；p = 0.003) 或厄洛替尼 (23%；p = 0.002)。与阿法替尼（1% vs 2%；p<0.001）或厄洛替尼（2%；p=0.004）相比，osi 因 AE 导致的停药率较低。在一项大型现实分析中，osi 表现出优异的无进展生存期和总生存期与阿法替尼或厄洛替尼相比，对于非典型 EGFR 突变 mNSCLC 的耐受性得到改善。版权所有 © 2024。由 Elsevier B.V. 出版。

Limited data are available comparing the efficacy of osi versus earlier generation TKIs for mNSCLC with atypical EGFR mutations (AMs) such as L861Q, G719X, S768I and exon20.We performed a single-institution retrospective analysis of patients with EGFR-mutated mNSCLC treated from 2007 to 2023 with 1L TKIs, comparing outcomes for AM patients treated with osi, afatinib, and erlotinib. Baseline demographics, disease characteristics, treatment history, toxicity, and clinical outcomes were abstracted from the electronic medical record and compared between TKIs using independent sample t-tests and chi-square analyses. Median progression free survival (mPFS) and overall survival (mOS) were compared via Kaplan-Meier log-rank analysis and Cox multivariable regression.Among 355 patients with EGFR-mutated mNSCLC, 36 (10 %) harbored AMs in G719X (N=21; 6 %), Exon 20 (N=11; 3 %), L861Q (N=7; 2 %), S768I (N=4; 1 %), C797S (N=1; 0.3 %); 6 patients had compound mutations. Patients with classical mutations (CMs) vs AMs had similar baseline demographic and disease characteristics and usage of TKIs (p = 0.124). Among AM patients, osi yielded superior mPFS (22 m) vs afatinib (12 m; p = 0.005) or erlotinib (9 m; p = 0.001). mOS was likewise superior for osi (32 m) vs afatinib (21 m; p = 0.032) or erlotinib (17 m; p = 0.011). Dose-reduction rates due to AEs were lower for osi (19 %) vs afatinib (24 %; p = 0.003) or erlotinib (23 %; p = 0.002). Discontinuation rates due to AEs were lower for osi vs afatinib (1 % vs 2 %; p < 0.001) or erlotinib (2 %; p = 0.004).In a large real-world analysis, osi demonstrated superior progression-free and overall survival and improved tolerability compared to afatinib or erlotinib for atypical EGFR-mutated mNSCLC.Copyright © 2024. Published by Elsevier B.V.