Lee Jii Bum, Choi Su-Jin, Shim Hyo Sup, Park Byung Jo, Lee Chang Young, Sudhaman Sumedha, Velichko Sharlene, Hong Min Hee, Cho Byoung Chul, Lim Sun Min
Division of Medical Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea.
Department of Pathology, Yonsei University College of Medicine, Seoul, Republic of Korea.
J Thorac Oncol. 2025 May;20(5):641-650. doi: 10.1016/j.jtho.2024.12.023. Epub 2024 Dec 26.
Treatment with adjuvant osimertinib for three years is the standard-of-care for resected stage IB to IIIA NSCLC harboring EGFR mutations. The role of neoadjuvant osimertinib in the perioperative setting is yet to be elucidated in the NeoADAURA study (NCT04351555).
This is a single-center, pilot study of patients with clinical stage IA to IIIA NSCLC (American Joint Committee on Cancer eighth edition) harboring an activating EGFR mutation (Exon 19 deletion, L858R) (NCT04816838). Patients were treated with two 28-day cycles of neoadjuvant osimertinib followed by surgical resection and three years of adjuvant osimertinib. The primary endpoint was the objective response rate after two cycles of neoadjuvant treatment. Secondary endpoints included the pathologic complete response rate and major pathologic response rate. Exploratory objectives included the correlation of longitudinal circulating tumor DNA testing (Signatera) and response to neoadjuvant osimertinib.
A total of 25 patients were enrolled and treated with neoadjuvant osimertinib, and all patients received surgical resection with R0 resection. The objective response rate was 44% (n = 11) all of which were partial responses. Fourteen patients (56%) reported stable disease after neoadjuvant osimertinib. The major pathologic response and pathologic complete response rates were 24% (n = 6) and 0%, respectively. None of the patients received adjuvant chemotherapy. The median disease-free survival was not reached at a median follow-up of 31 months (range: 13.8-38.6 mo). Six patients (30%) were circulating tumor DNA-positive at baseline and achieved clearance after 1 cycle of neoadjuvant osimertinib. There were no grade 3 adverse events during neoadjuvant treatment.
Two cycles of neoadjuvant osimertinib did not meet its primary endpoint of ORR. Neoadjuvant osimertinib is a feasible approach with a manageable safety profile in resectable EGFR-mutant NSCLC.
对于切除的伴有表皮生长因子受体（EGFR）突变的IB至IIIA期非小细胞肺癌（NSCLC）患者，辅助使用奥希替尼治疗三年是标准治疗方案。新辅助奥希替尼在围手术期的作用在NeoADAURA研究（NCT04351555）中尚未阐明。
这是一项针对临床IA至IIIA期NSCLC（美国癌症联合委员会第八版）且伴有激活型EGFR突变（外显子19缺失、L858R）患者的单中心试点研究（NCT04816838）。患者接受两个28天周期的新辅助奥希替尼治疗，随后进行手术切除，并接受三年的辅助奥希替尼治疗。主要终点是新辅助治疗两个周期后的客观缓解率。次要终点包括病理完全缓解率和主要病理缓解率。探索性目标包括纵向循环肿瘤DNA检测（Signatera）与新辅助奥希替尼反应的相关性。
共有25例患者入组并接受新辅助奥希替尼治疗，所有患者均接受了R0切除的手术切除。客观缓解率为44%（n = 11），均为部分缓解。14例患者（56%）在新辅助奥希替尼治疗后报告疾病稳定。主要病理缓解率和病理完全缓解率分别为24%（n = 6）和0%。所有患者均未接受辅助化疗。在中位随访31个月（范围：13.8 - 38.6个月）时，无病生存期未达到中位值。6例患者（30%）在基线时循环肿瘤DNA呈阳性，在新辅助奥希替尼治疗1个周期后实现清除。新辅助治疗期间无3级不良事件发生。
两个周期的新辅助奥希替尼未达到其客观缓解率的主要终点。新辅助奥希替尼是一种可行的方法，在可切除的EGFR突变NSCLC中安全性可控。
