Division of Hematology/Oncology, Department of Medicine, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA.
Division of Hematology/Oncology, Department of Medicine, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA.
Lung Cancer. 2024 Sep;195:107926. doi: 10.1016/j.lungcan.2024.107926. Epub 2024 Aug 10.
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.
目前可用的数据有限，无法比较 osi 与早期一代 TKI 治疗具有非典型 EGFR 突变（如 L861Q、G719X、S768I 和外显子 20）的 mNSCLC 的疗效。
我们对 2007 年至 2023 年期间接受 1L TKI 治疗的 EGFR 突变型 mNSCLC 患者进行了单机构回顾性分析，比较了 AM 患者接受 osi、阿法替尼和厄洛替尼治疗的结果。从电子病历中提取患者的基线人口统计学、疾病特征、治疗史、毒性和临床结局，并使用独立样本 t 检验和卡方分析比较 TKI 之间的差异。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 例 EGFR 突变型 mNSCLC 患者中，36 例（10%）存在 G719X（N=21；6%）、外显子 20（N=11；3%）、L861Q（N=7；2%）、S768I（N=4；1%）、C797S（N=1；0.3%）的 AM；6 例患者存在复合突变。具有经典突变（CMs）的患者与 AMs 具有相似的基线人口统计学和疾病特征以及 TKI 使用率（p=0.124）。在 AM 患者中，osi 的 mPFS 优于阿法替尼（22m）（p=0.005）或厄洛替尼（9m）（p=0.001）。osi 的 mOS 也优于阿法替尼（32m）（p=0.032）或厄洛替尼（17m）（p=0.011）。由于不良反应而降低剂量的发生率，osi 组（19%）低于阿法替尼组（24%）（p=0.003）或厄洛替尼组（23%）（p=0.002）。由于不良反应而停药的发生率，osi 组（1%）低于阿法替尼组（2%）（p<0.001）或厄洛替尼组（2%）（p=0.004）。
在一项大型真实世界分析中，osi 与阿法替尼或厄洛替尼相比，在具有非典型 EGFR 突变的 mNSCLC 患者中显示出更好的无进展生存期和总生存期，并具有更好的耐受性。
