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

Dr. Anjan Patel's Thoughts

New 3^rd 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

Amivantamab plus Lazertinib in Previously Untreated EGFR-Mutated Advanced NSCLC

Superior to osi (23 vs 16 progression-free survival). This is more toxic though, but seems manageable. Could this be a new first line standard of care? Also, this includes brain penetration data.

Tyrosine Kinase Inhibitors With and Without Up-Front Stereotactic Radiosurgery for Brain Metastases From EGFR and ALK Oncogene–Driven Non–Small Cell Lung Cancer (TURBO-NSCLC)

Adding SBRT improves local control and disease progression in the brain but not overall survival. Do the radiation oncologists have input? Is it worth it to control symptoms?

Neoadjuvant Osimertinib for the Treatment of Stage I-IIIA Epidermal Growth Factor Receptor–Mutated Non–Small Cell Lung Cancer: A Phase II Multicenter Study

Neoadjuvant Osimertinib did not have a significant impact on major pathologic response and there were no ypCR’s after a median of ~8 weeks of therapy. I do think this shows a measurable response, enough such that I would consider Osi in a patient with “borderline resectable” disease.

Ivonescimab Plus Chemotherapy in Non–Small Cell Lung Cancer With EGFR Variant – A Randomized Clinical Trial

Bispecific (a bispecific antibody targeting programmed cell death 1 protein and vascular endothelial growth factor) and chemotherapy … and it worked … second line after EGFR therapy failure.

Osimertinib after Chemoradiotherapy in Stage III EGFR-Mutated NSCLC

Osimertinib in adjuvant, now after chemotherapy and radiation, next… Neoadjuvant??? Trials are ongoing.

This is here till progression.