一线使用奥希替尼治疗的EGFR突变型晚期非小细胞肺癌的总生存期：美国一项整合临床和生物标志物数据的队列研究

Overall Survival in EGFR-Mutant Advanced NSCLC Treated With First-Line Osimertinib: A Cohort Study Integrating Clinical and Biomarker Data in the United States.

作者信息

Sabari Joshua K, Yu Helena A, Mahadevia Parthiv J, Liu Yanfang, Demirdjian Levon, Chen Yen Hua, Wang Xiayi, Passaro Antonio

机构信息

Perlmutter Cancer Center, New York University Langone Health, New York, New York.

Memorial Sloan Kettering Cancer Center, New York, New York.

出版信息

J Thorac Oncol. 2025 May 2. doi: 10.1016/j.jtho.2025.04.010.

DOI:10.1016/j.jtho.2025.04.010

PMID:40320171

Abstract

INTRODUCTION

Patients with NSCLC harboring EGFR mutations (EGFRm) have high mortality. The third-generation tyrosine kinase inhibitor, osimertinib, is approved for first-line EGFRm NSCLC. We used longitudinal U.S. medical oncology databases to evaluate real-world overall survival (rwOS) and prognostic risk factor groups in advanced EGFRm NSCLC treated with first-line osimertinib.

METHODS

This retrospective, new-user cohort study used electronic records from ConcertAI, Flatiron Clinical-Genomics, and COTA databases. Patients with advanced or metastatic EGFRm NSCLC initiating osimertinib monotherapy in first line between April 1, 2018, and October 30, 2022, were included. Follow-up was until death or October 31, 2023. rwOS was estimated using the Kaplan-Meier method. Risk factors were evaluated using multivariate analysis.

RESULTS

A total of 1323 patients were included with a median follow-up of 20 months. Median age was 70 (range 35-89) years. Median rwOS was 28.6 months (95% confidence interval 26.8-30.9). In high-risk subgroups, median rwOS (mo) was 18.1 in patients with Eastern Cooperative Oncology Group score greater than or equal to 2, 24.3 with brain metastases, 19.3 with liver metastases, and 25.7 with TP53 co-mutation. In total, 95% of patients had at least one high-risk factor. Prevalence of Eastern Cooperative Oncology Group greater than or equal to 2 was 17%, brain metastases 36%, liver metastases 15%, and TP53 co-mutation 63%. Risk of death was significantly higher in patients with high-risk factors (p ≤ 0.011 for all). In total, 58% of patients survived to 2 years, 18% to 5 years, and 33% did not receive second-line therapy.

CONCLUSION

Despite advances in tyrosine kinase inhibitor treatments, long-term survival of patients with advanced EGFRm NSCLC remains poor. Nearly all patients had risk factors for mortality and one-third did not receive second-line therapy.

摘要

引言

携带表皮生长因子受体（EGFR）突变（EGFRm）的非小细胞肺癌（NSCLC）患者死亡率很高。第三代酪氨酸激酶抑制剂奥希替尼已被批准用于一线治疗EGFRm NSCLC。我们利用美国纵向医学肿瘤学数据库评估了接受一线奥希替尼治疗的晚期EGFRm NSCLC患者的真实世界总生存期（rwOS）和预后风险因素组。

方法

这项回顾性新用户队列研究使用了ConcertAI、Flatiron临床基因组学和COTA数据库中的电子记录。纳入了2018年4月1日至2022年10月30日期间开始一线使用奥希替尼单药治疗的晚期或转移性EGFRm NSCLC患者。随访至死亡或2023年10月31日。使用Kaplan-Meier方法估计rwOS。通过多变量分析评估风险因素。

结果

共纳入1323例患者，中位随访时间为20个月。中位年龄为70岁（范围35 - 89岁）。中位rwOS为28.6个月（95%置信区间26.8 - 30.9）。在高风险亚组中，东部肿瘤协作组（ECOG）评分大于或等于2的患者中位rwOS为18.1个月，有脑转移的患者为24.3个月，有肝转移的患者为19.3个月，有TP53共突变的患者为25.7个月。总体而言，95%的患者至少有一个高风险因素。ECOG评分大于或等于2的患病率为17%，脑转移为36%，肝转移为15%，TP53共突变为63%。有高风险因素的患者死亡风险显著更高（所有p≤0.011）。总体而言，58%的患者存活至2年，18%存活至5年，33%未接受二线治疗。