Abstract CT053: Aumolertinib with or without chemotherapy as first line treatment in locally advanced or metastatic NSCLC with sensitizing EGFR mutations (AENEAS2)

Abstract Introduction: Aumolertinib, a third generation selective EGFR-TKI, is standard of care for the first-line treatment in advanced or metastatic NSCLC with sensitizing EGFR mutations in China. Evidence has shown that combining EGFR-TKIs with chemotherapy can improve outcomes compared to EGFR-TKIs monotherapy. AENEAS2 (NCT04923906) is a randomized, open-label, multicenter, phase 3 study assessing the efficacy and safety of aumolertinib plus chemotherapy versus aumolertinib alone as first-line treatment in locally advanced or metastatic NSCLC with sensitizing EGFR mutations. Methods: Patients who were naïve to treatment with locally advanced or metastatic NSCLC harboring EGFR mutations (exon 19 deletion or L858R mutation) were randomly assigned in a 1:1 ratio to receive aumolertinib 110 mg QD in combination with pemetrexed (500 mg/m2) plus cisplatin (75 mg/m2) or carboplatin (AUC5), versus to receive aumolertinib 110 mg QD monotherapy. The primary endpoint is progression free survival (PFS) assessed by IRC (Independent Review Committee) per RECIST v1.1. Data cutoff date: 2024/06/18. Results: A total of 624 patients were randomized to aumolertinib plus chemotherapy (n=310) or aumolertinib monotherapy (n=314) and stratified according to EGFR mutation status (Ex19del verse L858R) and CNS metastases at baseline (yes versus no). Baseline characteristics were balanced between treatment arms (aumolertinib plus chemotherapy versus aumolertinib): median age (range), 58.0 (30-84)/59.0 (31-81) years; 55.5/52.5 % female; 49.0/49.0% Ex19del; 51.0/51.0% L858R; 30.0/30.9% CNS metastases. Median follow-up was 23.4 months. Median PFS assessed by IRC was 28.9 months (95% CI, 26.3 to NA) in combination arm versus 18.9 months (95% CI, 17.8 to 21.1) in monotherapy arm; hazard ratio (HR) 0.471 (95% CI, 0.371 to 0.598; p<0.0001). The PFS benefit was consistent across pre-defined subgroups. The overall survival (OS) was immature with event-patient rate 21.6%; HR 0.442 (95% CI, 0.308 to 0.636; p<0.0001). Median cycles of pemetrexed exposure (range) were 20.0 (1-42) cycles, 88.8% of patients completed 4∼6 cycles of platinum therapy. All causality grade ≥3 AEs (aumolertinib plus chemotherapy versus aumolertinib): 75.7%/23.7%; AEs leading to discontinuation of aumolertinib: 3.0%/1.3%. The safety profile of aumolertinib plus pemetrexed and platinum was consistent with the established profiles of the individual agent. Conclusion: Aumolertinib plus chemotherapy as a first-line treatment in advanced EGFR-mutant NSCLC demonstrated a statistically significant and clinically meaningful PFS improvement over aumoletinib monotherapy, with a manageable safety profile. Citation Format: Shun Lu, Jie Hu, Jianhua Chen, Yan Yu, Xiangjiao Meng, Xiaorong Dong, Yanping Hu, Yinghua Ji, Ying Cheng, Weibo Wang, Fangling Ning, Zhihong Zhang, Zhiye Zhang, Chunling Liu, Qiming Wang, Wei Zheng, Xiujuan Qu, Honghai Wang, Runxiang Yang, Renhua Guo, Jianhua Shi, Feng Wu, Dongqing Lv, Jian Fang, Zhi Xu, Huaqiu Shi, Haichuan Su, Yongxing Chen, Cheng zhi Zhou, Junhong Zhang, Xuewen Liu, Zhaoxia Dai, Wen Li, Zili Meng, Guojun Zhang, Biyong Ren, Lin Wu, Yalun Li, Xinmin Yu, Ziping Wang, Jian Feng, Yueyin Pan, Juan Li, Xiangdong Zhou, Suxian Hu, Tongmei Zhang, Laiyu Liu, Jiming Shen, Shaonan Fan, Zhenming Chen. Aumolertinib with or without chemotherapy as first line treatment in locally advanced or metastatic NSCLC with sensitizing EGFR mutations (AENEAS2) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_2):Abstract nr CT053.

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Cancer Research
Published
2025-04-25
DOI
https://doi.org/10.1158/1538-7445.am2025-ct053
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3
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Lung Cancer Treatments and Mutations
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article
Field-Weighted Citation Impact
4.56
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Abstract CT053: Aumolertinib with or without chemotherapy as first line treatment in locally advanced or metastatic NSCLC with sensitizing EGFR mutations (AENEAS2)

Yueyin Pan, Chengzhi Zhou, Xiangjiao Meng, Haichuan Su et al.
3 citations
Cancer Research
Lung Cancer Treatments and Mutations
4.56
article

Abstract CT053: Aumolertinib with or without chemotherapy as first line treatment in locally advanced or metastatic NSCLC with sensitizing EGFR mutations (AENEAS2)

Yueyin Pan, Chengzhi Zhou, Xiangjiao Meng, Haichuan Su, Zhiye Zhang, Jian Feng, Zhenming Chen, Jie Hu, Fangling Ning, Laiyu Liu, Yanping Hu, Dongqing Lv, Xiaorong Dong, Renhua Guo, Xiangdong Zhou, Wen Li, Guojun Zhang, Jianhua Chen, Jun Zhang, Zhihong Zhang, Qiming Wang, Chunling Liu, Xinmin Yu, Jianhua Shi, Biyong Ren, Xiujuan Qu, Weibo Wang, Honghai Wang, Zili Meng, Zhi Xu, Yalun Li, Runxiang Yang, Wei Zheng, Ziping Wang, Yinghua Ji, Zhaoxia Dai, Juan Li, Jian Fang, Yongxing Chen, Feng Wu, Tongmei Zhang, Shaonan Fan, Yan Yu, Suxian Hu, Lin Wu, Jiming Shen, Ying Cheng, Shun Lu, Xuewen Liu, Huaqiu Shi
article en
3 citations

Abstract

Abstract Introduction: Aumolertinib, a third generation selective EGFR-TKI, is standard of care for the first-line treatment in advanced or metastatic NSCLC with sensitizing EGFR mutations in China. Evidence has shown that combining EGFR-TKIs with chemotherapy can improve outcomes compared to EGFR-TKIs monotherapy. AENEAS2 (NCT04923906) is a randomized, open-label, multicenter, phase 3 study assessing the efficacy and safety of aumolertinib plus chemotherapy versus aumolertinib alone as first-line treatment in locally advanced or metastatic NSCLC with sensitizing EGFR mutations. Methods: Patients who were naïve to treatment with locally advanced or metastatic NSCLC harboring EGFR mutations (exon 19 deletion or L858R mutation) were randomly assigned in a 1:1 ratio to receive aumolertinib 110 mg QD in combination with pemetrexed (500 mg/m2) plus cisplatin (75 mg/m2) or carboplatin (AUC5), versus to receive aumolertinib 110 mg QD monotherapy. The primary endpoint is progression free survival (PFS) assessed by IRC (Independent Review Committee) per RECIST v1.1. Data cutoff date: 2024/06/18. Results: A total of 624 patients were randomized to aumolertinib plus chemotherapy (n=310) or aumolertinib monotherapy (n=314) and stratified according to EGFR mutation status (Ex19del verse L858R) and CNS metastases at baseline (yes versus no). Baseline characteristics were balanced between treatment arms (aumolertinib plus chemotherapy versus aumolertinib): median age (range), 58.0 (30-84)/59.0 (31-81) years; 55.5/52.5 % female; 49.0/49.0% Ex19del; 51.0/51.0% L858R; 30.0/30.9% CNS metastases. Median follow-up was 23.4 months. Median PFS assessed by IRC was 28.9 months (95% CI, 26.3 to NA) in combination arm versus 18.9 months (95% CI, 17.8 to 21.1) in monotherapy arm; hazard ratio (HR) 0.471 (95% CI, 0.371 to 0.598; p<0.0001). The PFS benefit was consistent across pre-defined subgroups. The overall survival (OS) was immature with event-patient rate 21.6%; HR 0.442 (95% CI, 0.308 to 0.636; p<0.0001). Median cycles of pemetrexed exposure (range) were 20.0 (1-42) cycles, 88.8% of patients completed 4∼6 cycles of platinum therapy. All causality grade ≥3 AEs (aumolertinib plus chemotherapy versus aumolertinib): 75.7%/23.7%; AEs leading to discontinuation of aumolertinib: 3.0%/1.3%. The safety profile of aumolertinib plus pemetrexed and platinum was consistent with the established profiles of the individual agent. Conclusion: Aumolertinib plus chemotherapy as a first-line treatment in advanced EGFR-mutant NSCLC demonstrated a statistically significant and clinically meaningful PFS improvement over aumoletinib monotherapy, with a manageable safety profile. Citation Format: Shun Lu, Jie Hu, Jianhua Chen, Yan Yu, Xiangjiao Meng, Xiaorong Dong, Yanping Hu, Yinghua Ji, Ying Cheng, Weibo Wang, Fangling Ning, Zhihong Zhang, Zhiye Zhang, Chunling Liu, Qiming Wang, Wei Zheng, Xiujuan Qu, Honghai Wang, Runxiang Yang, Renhua Guo, Jianhua Shi, Feng Wu, Dongqing Lv, Jian Fang, Zhi Xu, Huaqiu Shi, Haichuan Su, Yongxing Chen, Cheng zhi Zhou, Junhong Zhang, Xuewen Liu, Zhaoxia Dai, Wen Li, Zili Meng, Guojun Zhang, Biyong Ren, Lin Wu, Yalun Li, Xinmin Yu, Ziping Wang, Jian Feng, Yueyin Pan, Juan Li, Xiangdong Zhou, Suxian Hu, Tongmei Zhang, Laiyu Liu, Jiming Shen, Shaonan Fan, Zhenming Chen. Aumolertinib with or without chemotherapy as first line treatment in locally advanced or metastatic NSCLC with sensitizing EGFR mutations (AENEAS2) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_2):Abstract nr CT053.

Cancer ResearchVol. 85(8_Supplement_2)
Binzhou Medical University (CN), Central South University (CN), Shandong University of Aeronautics (CN), Army Medical University (CN), Xinjiang Medical University (CN), Harbin Medical University (CN), Chongqing University (CN), Capital Medical University (CN), Dalian Medical University (CN), Nantong University (CN), Peking University (CN), Sichuan University (CN), Fudan University (CN), Kunming Medical University (CN), Wenzhou Medical University (CN), Shanghai Chest Hospital (CN), Wuhan University (CN), Zhengzhou University (CN), Affiliated Hospital of Nantong University (CN), First Affiliated Hospital of Xiamen University (CN), People 's Liberation Army 451 Hospital (CN), West China Hospital of Sichuan University (CN), Peking University Cancer Hospital (CN), Huaian First People’s Hospital (CN), First Affiliated Hospital of Guangzhou Medical University (CN), Jilin Province Tumor Hospital (CN), Shandong Tumor Hospital (CN), Second Affiliated Hospital of Dalian Medical University (CN), Nanfang Hospital (CN), Beijing Chest Hospital (CN), Hunan Cancer Hospital (CN), Shandong Provincial Hospital (CN), Xinqiao Hospital (CN), Sichuan Cancer Hospital (CN), Zhongnan Hospital of Wuhan University (CN), Zhongshan Hospital (CN), Hainan General Hospital (CN), Anhui Provincial Hospital (CN), First Affiliated Hospital of Gannan Medical University (CN), First Affiliated Hospital of Henan University of Science and Technology (CN), First Hospital of China Medical University (CN), Henan Cancer Hospital (CN), Jiangsu Province Hospital (CN), First Affiliated Hospital of Zhengzhou University (CN), Third Xiangya Hospital (CN), Second Affiliated Hospital of Zhejiang University (CN), Zhejiang Taizhou Hospital (CN), Hubei Cancer Hospital (CN), Anyang Tumor Hospital (CN), Shandong First Medical University (CN), Union Hospital (CN), Hangzhou Cancer Hospital (CN), Huazhong University of Science and Technology (CN), Yangzhou University (CN), China Medical University (CN), Guangzhou Medical University (CN)
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