Central nervous system efficacy of aumolertinib versus gefitinib in patients with untreated, <i>EGFR</i> ‐mutated, advanced non‐small cell lung cancer: data from a randomized phase III trial (AENEAS)
Shun Lü, Xiaorong Dong, Hong Jian, Jianhua Chen, Gongyan Chen, Yuping Sun, Yinghua Ji, Ziping Wang, Jianhua Shi, Junguo Lu, Shaoshui Chen, Dongqing Lv, Guojun Zhang, Chunling Liu, Juan Li, Xinmin Yu, Lin Zhong, Zhuang Yu, Zhehai Wang, Jiuwei Cui, Xingxiang Xu, Jian Fang, Ji‐Feng Feng, Zhixiang Xu, Rui Ma, Jie Hu, Nong Yang, Xiangdong Zhou, Xiaohong Wu, Chengping Hu, Zhihong Zhang, You Lu, Yanping Hu, Liyan Jiang, Q. Wang, Renhua Guo, Jianying Zhou, Baolan Li, Chunhong Hu, Wan-cheng Tong, Helong Zhang, Lin Ma, Yuan Chen, Zhijun Jie, Yao Yu, Longzhen Zhang, Jie Weng, Weidong Li, Jianping Xiong, Xianwei Ye, Jianchun Duan, Haihua Yang, Meili Sun, Hongying Wei, Jiawei Wei, Zheyu Zhang, Qiong Wu
Abstract
BACKGROUND: The initial randomized, double-blinded, actively controlled, phase III ANEAS study (NCT03849768) demonstrated that aumolertinib showed superior efficacy relative to gefitinib as first-line therapy in epidermal growth factor receptor (EGFR)-mutated advanced non-small cell lung cancer (NSCLC). Metastatic disease in the central nervous system (CNS) remains a challenge in the management of NSCLC. This study aimed to compare the efficacy of aumolertinib versus gefitinib among patients with baseline CNS metastases in the ANEAS study. METHODS: Eligible patients were enrolled and randomly assigned in a 1:1 ratio to orally receive either aumolertinib or gefitinib in a double-blinded fashion. Patients with asymptomatic, stable CNS metastases were included. Follow-up imaging of the same modality as the initial CNS imaging was performed every 6 weeks for 15 months, then every 12 weeks. CNS response was assessed by a neuroradiological blinded, independent central review (neuroradiological-BICR). The primary endpoint for this subgroup analysis was CNS progression-free survival (PFS). RESULTS: Of the 429 patients enrolled and randomized in the ANEAS study, 106 patients were found to have CNS metastases (CNS Full Analysis Set, cFAS) at baseline by neuroradiological-BICR, and 60 of them had CNS target lesions (CNS Evaluable for Response, cEFR). Treatment with aumolertinib significantly prolonged median CNS PFS compared with gefitinib in both cFAS (29.0 vs. 8.3 months; hazard ratio [HR] = 0.31; 95% confidence interval [CI], 0.17-0.56; P < 0.001) and cEFR (29.0 vs. 8.3 months; HR = 0.26; 95% CI, 0.11-0.57; P < 0.001). The confirmed CNS overall response rate in cEFR was 85.7% and 75.0% in patients treated with aumolertinib and gefitinib, respectively. Competing risk analysis showed that the estimated probability of CNS progression without prior non-CNS progression or death was consistently lower with aumolertinib than with gefitinib in patients with and without CNS metastases at baseline. No new safety findings were observed. CONCLUSIONS: These results indicate a potential advantage of aumolertinib over gefitinib in terms of CNS PFS and the risk of CNS progression in patients with EGFR-mutated advanced NSCLC with baseline CNS metastases. TRIAL REGISTRATION: ClinicalTrials.gov number, NCT03849768.