一线奥希替尼与早期一代酪氨酸激酶抑制剂治疗晚期表皮生长因子受体（EGFR）突变非小细胞肺癌（NSCLC）的比较：一项真实世界生存分析

First-line osimertinib compared to earlier generation TKIs in advanced EGFR-mutant NSCLC: A real-world survival analysis.

作者信息

Gomez-Randulfe Igor, Scanlon Lauren A, Carter Mathew, Moliner Laura, Cil Emine, Califano Raffaele, Summers Yvonne, Blackhall Fiona, Lindsay Colin R, Lewis Jacob, Gomes Fabio

机构信息

Department of Medical Oncology The Christie NHS Foundation Trust Manchester UK.

Clinical Outcomes Data Unit The Christie NHS Foundation Trust Manchester UK.

出版信息

Lung Cancer. 2025 Feb;200:108084. doi: 10.1016/j.lungcan.2025.108084. Epub 2025 Jan 9.

DOI:10.1016/j.lungcan.2025.108084

PMID:39823701

Abstract

OBJECTIVES

This study aimed to compare the overall survival (OS) of patients with advanced EGFR-mutant NSCLC treated with first-line osimertinib versus earlier-generation EGFR tyrosine kinase inhibitors (TKIs) in a real-world setting. Secondary endpoint included OS in patients with uncommon EGFR mutations. Exploratory aim focused on the impact of TKIs sequencing strategies.

METHODS

We conducted a retrospective cohort study of patients diagnosed with advanced EGFR-mutant NSCLC who started first-line treatment with either osimertinib or another EGFR TKI (afatinib, erlotinib, or gefitinib) at The Christie (Manchester, UK) from January 2014 to May 2023. Data were extracted from electronic health records, and survival outcomes were analysed using Kaplan-Meier estimates and Cox proportional hazards models.

RESULTS

We identified 119 patients treated with first-line osimertinib and 217 with other EGFR TKIs. In the whole population, median age was 69 years (IQR 59.8-77) and 67.3 % of the patients had an ECOG 0-1. With a median follow-up of 73.2 months (95 % CI 66.2-115.7) and 30.6 months (95 % CI 26.0-38.4) in the earlier-generation TKIs and the osimertinib groups, respectively, the median OS was comparable (16.6 vs 16.9 months; HR = 1, p = 0.97). Patients with uncommon EGFR mutations (n = 48; 14.3 %) had poorer survival compared to those with common mutations (HR = 1.664, p = 0.002). Amongst patients who received two treatment lines, those who received osimertinib after another TKI had a shorter OS than those who received osimertinib first-line followed by another line of therapy (HR = 2.062, p = 0.022).

CONCLUSION

First-line osimertinib showed comparable OS to earlier-generation EGFR TKIs for advanced EGFR-mutant NSCLC. Patients with uncommon EGFR mutations had a poorer survival. Further research is warranted to optimize treatment for patients with uncommon EGFR mutations and to explore the cost-effectiveness of different sequencing approaches.

摘要

目的

本研究旨在比较在真实世界中，一线使用奥希替尼与早期一代表皮生长因子受体酪氨酸激酶抑制剂（EGFR-TKIs）治疗的晚期EGFR突变型非小细胞肺癌（NSCLC）患者的总生存期（OS）。次要终点包括罕见EGFR突变患者的总生存期。探索性目的聚焦于EGFR-TKIs序贯策略的影响。

方法

我们对2014年1月至2023年5月在英国曼彻斯特克里斯蒂医院被诊断为晚期EGFR突变型NSCLC并开始一线使用奥希替尼或其他EGFR-TKI（阿法替尼、厄洛替尼或吉非替尼）治疗的患者进行了一项回顾性队列研究。数据从电子健康记录中提取，生存结局使用Kaplan-Meier估计法和Cox比例风险模型进行分析。

结果

我们确定了119例接受一线奥希替尼治疗的患者和217例接受其他EGFR-TKIs治疗的患者。在总体人群中，中位年龄为69岁（四分位间距59.8 - 77岁），67.3%的患者东部肿瘤协作组（ECOG）评分为0 - 1。早期一代EGFR-TKIs组和奥希替尼组的中位随访时间分别为73.2个月（95%置信区间66.2 - 115.7）和30.6个月（95%置信区间26.0 - 38.4），中位总生存期相当（16.6个月对16.9个月；风险比[HR]=1，p = 0.97）。与常见突变患者相比，罕见EGFR突变患者（n = 48；14.3%）的生存期更短（HR = 1.664，p = 0.002）。在接受两线治疗的患者中，在接受另一种TKI后再接受奥希替尼治疗的患者的总生存期短于一线接受奥希替尼治疗后再接受另一线治疗的患者（HR = 2.062，p = 0.022）。