AENEAS: A Randomized Phase III Trial of Aumolertinib Versus Gefitinib as First-Line Therapy for Locally Advanced or Metastatic Non–Small-Cell Lung Cancer With EGFR Exon 19 Deletion or L858R Mutations

Author(s): Shun Lu, MD1;Xiaorong Dong, MD, PhD2;Hong Jian, MD1;Jianhua Chen, MD3;Gongyan Chen, MD, PhD4;Yuping Sun, MD, PhD5;Yinghua Ji, MD, PhD6;Ziping Wang, MD, PhD7;Jianhua Shi, MD8;Junguo Lu, MD9;Shaoshui Chen, MD10;Dongqing Lv, MD11;Guojun Zhang, MD, PhD12;Chunling Liu, MD13;Juan Li, MD, PhD14;Xinmin Yu, MD15;Zhong Lin, MD16;Zhuang Yu, MD, PhD17;Zhehai Wang, MD18;Jiuwei Cui, MD, PhD19;Xingxiang Xu, MD20;Jian Fang, MD7;Jifeng Feng, MD, PhD21;Zhi Xu, MD, PhD22;Rui Ma, MD, PhD23;Jie Hu, MD, PhD24;Nong Yang, MD25;Xiangdong Zhou, MD, PhD26;Xiaohong Wu, MD27;Chengping Hu, MD, PhD28;Zhihong Zhang, MD, PhD29;You Lu, MD, PhD30;Yanping Hu, MD31;Liyan Jiang, MD, PhD32;Qiming Wang, MD, PhD33;Renhua Guo, MD, PhD34;Jianying Zhou, MD35;Baolan Li, MD, PhD36;Chunhong Hu, MD, PhD37;Wancheng Tong, MD, PhD38;Helong Zhang, MD, PhD39;Lin Ma, MD40;Yuan Chen, MD, PhD41;Zhijun Jie, MD, PhD42;Yu Yao, MD, PhD43;Longzhen Zhang, MD44;Weng Jie, MD45;Weidong Li, MD, PhD46;Jianping Xiong, MD47;Xianwei Ye, MD, PhD48;Jianchun Duan, MD49;Haihua Yang, MD50;Meili Sun, MD, PhD51;Changan Sun, MSc52;Hongying Wei, MD, PhD52;Chuan Li, MD52;Siraj M. Ali, MD, PhD53;Vincent A. Miller, MD53;and Qiong Wu, MD, PhD52
Source: DOI: 10.1200/JCO.21.02641 Journal of Clinical Oncology 40, no. 27
Anjan J Patel MD

Dr. Anjan Patel's Thoughts

New 3rd gen TKI in EGFR+ patients to consider with strong efficacy, only available in China currently.   Shows again that ORR is not better with the newer drug, rather its more the duration of response which is far superior.

PURPOSE

Aumolertinib (formerly almonertinib; HS-10296) is a novel third-generation epidermal growth factor receptor tyrosine kinase inhibitor approved in China. This double-blind phase III trial evaluated the efficacy and safety of aumolertinib compared with gefitinib as a first-line treatment for locally advanced or metastatic EGFR-mutated non–small-cell lung cancer (NSCLC; ClinicalTrials.gov identifier: NCT03849768).

METHODS

Patients at 53 sites in China were randomly assigned 1:1 to receive either aumolertinib (110 mg) or gefitinib (250 mg) once daily. The primary end point was progression-free survival (PFS) per investigator assessment.

RESULTS

A total of 429 patients who were naïve to treatment for locally advanced or metastatic NSCLC were enrolled. PFS was significantly longer with aumolertinib compared with gefitinib (hazard ratio, 0.46; 95% CI, 0.36 to 0.60; P < .0001). The median PFS with aumolertinib was 19.3 months (95% CI, 17.8 to 20.8) versus 9.9 months with gefitinib (95% CI, 8.3 to 12.6). Objective response rate and disease control rate were similar in the aumolertinib and gefitinib groups (objective response rate, 73.8% and 72.1%, respectively; disease control rate, 93.0% and 96.7%, respectively). The median duration of response was 18.1 months (95% CI, 15.2 to not applicable) with aumolertinib versus 8.3 months (95% CI, 6.9 to 11.1) with gefitinib. Adverse events of grade ≥ 3 severity (any cause) were observed in 36.4% and 35.8% of patients in the aumolertinib and gefitinib groups, respectively. Rash and diarrhea (any grade) were observed in 23.4% and 16.4% of patients who received aumolertinib compared with 41.4% and 35.8% of those who received gefitinib, respectively.

CONCLUSION

Aumolertinib is a well-tolerated third-generation epidermal growth factor receptor tyrosine kinase inhibitor that could serve as a treatment option for EGFR-mutant NSCLC in the first-line setting.

Author Affiliations

1Department of Medical Oncology, Shanghai Chest Hospital, Shanghai JiaoTong University, Shanghai, China;2Cancer Center, Union Hospital Tongji Medical College Huazhong University of Science and Technology, Wuhan, China;3Department of Medical Oncology-Chest, Hunan Cancer Hospital & The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China;4Thoracic Oncology Medicine, Harbin Medical University Cancer Hospital, Harbin, China;5Department of Oncology, Jinan Central Hospital, Jinan, China;6Department of Oncology, First Affiliated Hospital of Xinxiang Medical University, Xinxiang, China;7Department of Chest Medicine, Beijing Cancer Hospital, Beijing, China;8Department of Internal Medicine, Linyi Cancer Hospital, Linyi, China;9Departments of Respiratory Medicine, Nantong Tumor Hospital, Nantong, China;10Department of Oncology, Binzhou Medical University Hospital, Binzhou, China;11Breath Internal Medicine, Taizhou Hospital of Zhejiang Province, Linhai, China;12Department of Respiration, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China;13Department of Lung Internal Medicine, Affiliated Tumor Hospital of Xinjiang Medical University, Urumqi, China;14Department of Thoracic Oncology, Sichuan Cancer Hospital, Chengdu, China;15Thoracic Medical Oncology, Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Hangzhou, China;16Department of Thoracic Oncology, The Fifth Subsidiary Sun Yat-sen University Hospital, Zhuhai, China;17Department of Oncology, The Affiliated Hospital of Qingdao University, Qingdao, China;18Department of Oncology, Shandong Cancer Hospital, Jinan, China;19Department of Oncology, The First Bethune Hospital of Jilin University, Changchun, China;20Department of Respiration, Northern Jiangsu People’s Hospital, The Affiliated Hospital to Yangzhou University, Yangzhou, China;21Department of Internal Medicine, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, China;22Department of Respiration, Xinqiao Hospital, The Second Affiliated Hospital of China PLA Army Medical University, Chongqing, China;23Department of Chest Internal Medicine, Liaoning Cancer Hospital & Institute, Shenyang, China;24Respiratory Medicine, Zhongshan Hospital, Fudan University, Shanghai, China;25Lung & Gastrointestinal Oncology Department, Hunan Cancer Hospital (The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University), Changsha, China;26Department of Respiratory and Critical Care Medicine, the Southwest Hospital of AMU, The First Affiliated Hospital of PLA Army Medical University, Chongqing, China;27Department of Oncology, Affiliated Hospital of Jiangnan University, Wuxi, China;28Respiratory Medicine, Xiangya Hospital Central South University, Changsha, China;29Department of Respiration Oncology, Anhui Provincial Cancer Hospital, Hefei, China;30Department of Thoracic Oncology, West China Hospital of Sichuan University, Chengdu, China;31Department of Thoracic Oncology, Hubei Cancer Hospital, Wuhan, China;32Department of Respiration, Shanghai Chest Hospital, Shanghai JiaoTong University, Shanghai, China;33Department of Respiration, Henan Cancer Hospital, Zhengzhou, China;34Department of Oncology, Jiangsu Province Hospital, Nanjing, China;35Department of Respiratory Medicine, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China;36Department of Oncology Internal Medicine, Beijing Chest Hospital, Capital Medical Hospital, Beijing, China;37Department of Oncology, Xiangya Second Hospital of Central South University, Changsha, China;38Department of Infection Internal Medicine, Nanfang Hospital, Nanfang Medical University, Guangzhou, China;39Department of Oncology, The Second Affiliated Hospital of Air Force Military Medical University, Xi’An, China;40Department of Respiration, The First Affiliated Hospital of Nanchang University, Nanchang, China;41Department of Oncology, Tongji Medical College Huazhong University of Science & Technology, Wuhan, China;42Department of Respiratory and Critical Care Medicine, Shanghai Fifth People’s Hospital, Fudan University Shanghai, China;43Department of Oncology Internal Medicine, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’An, China;44Radiotherapy Department, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China;45Department of Oncology, Yueyang Central Hospital, Yueyang, China;46Department of Internal Medicine, Affiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou, China;47Department of Oncology, The First Affiliated Hospital of Nanchang University, Nanchang, China;48Department of Respiratory and Critical Care Medicine, GuiZhou Provincial People’s Hospital, Guiyang, China;49Department of Internal Medicine, Cancer Hospital Chinese Academy of Medical Sciences, Beijing, China;50Radiotherapy Section, Taizhou Hospital of Zhejiang Province, Linhai, China;51Department of Oncology Internal Medicine, Jinan Central Hospital Affiliated to Shandong University, Jinan, China;52Hansoh Pharmaceutical Group Co. Ltd, Shanghai, China;53EQRx, Inc, Cambridge, MA

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