阿美替尼与奥希替尼一线治疗EGFR突变非小细胞肺癌：一项回顾性真实世界多中心研究
Aumolertinib Versus Osimertinib as First-Line Treatment for EGFR-Mutant Non-Small Cell Lung Cancer: A Retrospective Real-World Multicenter Study.
作者
作者单位
- The First Clinical Medical College of Lanzhou University, Lanzhou, China.
- Department of Oncology, The Second Hospital of Lanzhou University, Lanzhou, China.
- Department of Respiratory Oncology, Gansu Provincial Cancer Hospital, Lanzhou, China.
- Department of Thoracic Surgery, The First Hospital of Lanzhou University, Lanzhou, China.
- The Second Department of Radiotherapy, Gansu Provincial People's Hospital, Lanzhou, China.
- Medical Oncology Scientific Group of the Central Medical Department, Jiangsu Hansoh, Pharmaceutical Group co., Ltd., Shanghai, China.
- Department of Oncology, The First Hospital of Lanzhou University, Lanzhou, China.
摘要
中文
虽然第三代EGFR酪氨酸激酶抑制剂（TKIs）改善了EGFR突变NSCLC的预后，但这些药物之间的最优选择仍不确定。这项真实世界研究比较了阿美替尼和奥希替尼在一线治疗中的疗效和安全性。我们回顾性分析了来自四家三级医院（2016-2023年）的109例接受一线阿美替尼（n=53）或奥希替尼（n=56）治疗的EGFR突变（外显子19del/L858R）NSCLC患者。主要终点包括无进展生存期（PFS）和安全性；次要终点包括总生存期（OS）、客观缓解率（ORR）以及通过亚组分析识别预测性生物标志物。阿美替尼显示出优于奥希替尼的中位PFS（34.4 vs. 26.9个月；HR 0.52, 95% CI 0.29-0.92, p=0.031），OS相当（HR 0.76, 95% CI 0.27-2.15, p=0.60）。原发灶ORR（33.96%, 18/53 vs. 42.86%, 24/56）或不良事件（AE）发生率（37.7%, 20/53 vs. 39.3%, 22/56）无显著差异。亚组分析证实阿美替尼在外显子19del突变（HR 0.43, 95% CI 0.21-0.87, p=0.02）和共突变阴性（HR 0.53, 95% CI 0.25-1.14, p=0.08）人群中PFS获益增强。亚组分析确定年龄<65岁（HR 0.46, 95% CI 0.22-0.99, p=0.046）、脑转移（HR 0.24, 95% CI 0.09-0.66, p=0.006）和外显子19del状态（HR 0.43, 95% CI 0.2-0.89, p=0.023）为独立PFS预测因子。安全性方面，与奥希替尼相比，阿美替尼的肝功能异常总体发生率更低（9.43%, 5/53 vs. 14.29%, 8/56），≥3级事件罕见（1.89%, 1/53）。鉴于肝功能是预后的关键决定因素，阿美替尼可控的肝脏安全性支持其长期临床实用性。我们的研究表明，在未经治疗的EGFR突变NSCLC中，阿美替尼相比奥希替尼具有临床意义的PFS优势，尤其在外显子19del驱动和共突变阴性疾病中，同时保持等效安全性。这些发现为支持阿美替尼作为一线治疗提供了有价值的真实世界证据，有助于优化治疗选择和AE管理。虽然这些亚组特异性结果提供了关于治疗个体化潜在生物标志物的假设生成见解，但这些初步发现需要在更大规模的前瞻性队列中进一步验证。
English
While third-generation EGFR tyrosine kinase inhibitors (TKIs) improve outcomes in EGFR-mutant NSCLC, optimal selection between these agents remains uncertain. This real-world study compares the efficacy and safety of aumolertinib with those of osimertinib in the first-line treatment setting. We retrospectively analyzed 109 EGFR-mutant (exon 19del/L858R) NSCLC patients treated with first-line aumolertinib (n = 53) or osimertinib (n = 56) across four tertiary hospitals (2016-2023). The primary end points included progression-free survival (PFS) and safety; secondary end points encompassed overall survival (OS), objective response rate (ORR), and predictive biomarker identification through subgroup analyses. Aumolertinib demonstrated superior median PFS compared to osimertinib (34.4 vs. 26.9 months; HR 0.52, 95% CI 0.29-0.92, p = 0.031), with comparable OS (HR 0.76, 95% CI 0.27-2.15, p = 0.60). No significant differences emerged in primary lesion ORR (33.96%, 18/53 vs. 42.86%, 24/56) or adverse event (AE) rates (37.7%, 20/53 vs. 39.3%, 22/56). Subgroup analyses confirmed enhanced PFS benefit with aumolertinib in exon 19del-mutant (HR 0.43, 95% CI 0.21-0.87, p = 0.02) and co-mutation-negative (HR 0.53, 95% CI 0.25-1.14, p = 0.08) populations. Subgroup analysis identified age < 65 years (HR 0.46, 95% CI 0.22-0.99, p = 0.046), brain metastases (HR 0.24, 95% CI 0.09-0.66, p = 0.006), and exon 19del status (HR 0.43, 95% CI 0.2-0.89, p = 0.023) as independent PFS predictors. Regarding safety, aumolertinib showed a lower overall incidence of liver dysfunction compared to osimertinib (9.43%, 5/53 vs. 14.29%, 8/56), with Grade ≥ 3 events being rare (1.89%, 1/53). Given that liver function is a critical determinant of prognosis, the manageable hepatic safety profile of aumolertinib supports its long-term clinical utility. Our study demonstrated a clinically meaningful PFS advantage of aumolertinib over osimertinib in treatment-naïve EGFR-mutant NSCLC, particularly for exon 19del-driven and co-mutation-negative disease, while maintaining equivalent safety. These findings provide valuable real-world evidence supporting the use of aumolertinib as a first-line therapy, contributing to the optimization of treatment selection and AE management. While these subgroup-specific results offer hypothesis-generating insights into potential biomarkers for therapeutic individualization, these preliminary findings require further validation in larger, prospective cohorts.
分类与指标
- 研究类型
- 临床研究
- 病种
- 肺癌
- JCR 分区
- Q2
- 影响因子
- 4.9
- 新锐分区
- 2区