Yuankai Shi1, Xingsheng Hu2, Shucai Zhang3, Dongqing Lv4, Lin Wu5, Qitao Yu6, Yiping Zhang7, Li Liu8, Xiang Wang9, Ying Cheng10, Zhiyong Ma11, Hongrui Niu12, Dong Wang13, Jifeng Feng14, Cheng Huang15, Chunling Liu16, Hui Zhao17, Jingzhang Li18, Xiaodong Zhang19, Yong Jiang20, Chuan Gu20. 1. Department of Medical Oncology, Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs, National Cancer Center and National Clinical Research Center for Cancer and Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China. Electronic address: syuankai@cicams.ac.cn. 2. Department of Medical Oncology, Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs, National Cancer Center and National Clinical Research Center for Cancer and Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China. 3. Department of Oncology, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Oncology Institute, Beijing, China. 4. Department of Respiratory, Taizhou Hospital of Zhejiang Province, Taizhou, China. 5. Thoracic Medicine Department II, Hunan Cancer Hospital, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China. 6. Department of Medical Oncology of Respiratory, Guangxi Medical University Affiliated Tumor Hospital, Nanning, China. 7. Department of Medical Oncology, Zhejiang Cancer Hospital, Hangzhou, China. 8. Department of Thoracic Oncology, Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. 9. Department of Medical Oncology, Xuzhou Central Hospital, Xuzhou, China. 10. Jilin Cancer Hospital, Changchun, China. 11. Department of Medical Oncology, Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, China. 12. Department of Oncology, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, China. 13. Department of Oncology, Daping Hospital, Chongqing, China. 14. Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research, Nanjing Medical University Affiliated Cancer Hospital, Nanjing, China. 15. Fujian Cancer Hospital, Fuzhou, China. 16. Cancer Hospital of Xinjiang Medical University, Urumqi, China. 17. The Second Hospital Of Anhui University, Hefei, China. 18. Liuzhou People's Hospital, Liuzhou, China. 19. Department of Medical Oncology, Nantong Cancer Hospital, Nantong, China. 20. Shanghai Allist Pharmaceutical Technology, Shanghai, China.
Abstract
BACKGROUND: Furmonertinib (AST2818) is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) targeting both sensitising EGFR and EGFR Thr790Met (T790M) mutations. This study aimed to assess the efficacy and safety of furmonertinib in patients with EGFR T790M mutated advanced non-small-cell lung cancer (NSCLC). METHODS: This study was a single-arm, open-label, phase 2b study at 46 hospitals across mainland China. Patients with locally advanced or metastatic NSCLC with centrally confirmed EGFR T790M mutations in tumour tissue who progressed after first or second generation EGFR TKIs or with primary EGFR T790M mutations received furmonertinib 80 mg orally once daily. The primary endpoint was objective response rate. Efficacy was assessed by blinded independent central review as per the Response Evaluation Criteria in Solid Tumors (version 1.1) in all patients who had measurable disease at baseline and received at least one dose of furmonertinib. Safety was assessed as per the Common Terminology Criteria for Adverse Events (version 4.03) in all patients who received at least one dose of furmonertinib with at least one safety assessment during follow-up. This study is registered with ClinicalTrials.gov (NCT03452592) and is ongoing for survival follow-up. FINDINGS: From Jun 4, 2018, to Dec 8, 2018, 220 patients received furmonertinib treatment. All 220 patients were included in the efficacy and safety analyses. At the data cutoff point of Jan 29, 2020, 71 (32%) patients remained on treatment. The median duration of follow-up was 9·6 months (range 0·7-19·4). The objective response rate was 74% (163 of 220 [95% CI 68-80]). Grade 3 or higher adverse events occurred in 58 (26%) patients and treatment-related grade 3 or higher adverse events occurred in 25 (11%) patients. The most common all-cause grade 3 or higher adverse events were increased γ-glutamyltransferase (five; 2%), increased aspartate aminotransferase, increased alanine aminotransferase, hyponatraemia, hypertension, pulmonary infection, hypermagnesaemia, and pericardial effusion (three each; 1%). Treatment-related diarrhoea was reported in ten (5%) patients and rashes were reported in 16 (7%) patients, all grade 1-2. Serious adverse events were reported in 52 (24%) patients, of which 12 (5%) were possibly treatment-related as evaluated by the investigator. INTERPRETATION: Furmonertinib has promising efficacy and an acceptable safety profile for the treatment of patients with EGFR T790M mutated NSCLC. Furmonertinib is expected to become a new treatment option after first or second generation EGFR TKIs in the Chinese population. FUNDING: Shanghai Allist Pharmaceutical Technology, Ministry of Science and Technology of the People's Republic of China, and Chinese Academy of Medical Sciences. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.
BACKGROUND:Furmonertinib (AST2818) is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) targeting both sensitising EGFR and EGFR Thr790Met (T790M) mutations. This study aimed to assess the efficacy and safety of furmonertinib in patients with EGFRT790M mutated advanced non-small-cell lung cancer (NSCLC). METHODS: This study was a single-arm, open-label, phase 2b study at 46 hospitals across mainland China. Patients with locally advanced or metastatic NSCLC with centrally confirmed EGFRT790M mutations in tumour tissue who progressed after first or second generation EGFR TKIs or with primary EGFRT790M mutations received furmonertinib 80 mg orally once daily. The primary endpoint was objective response rate. Efficacy was assessed by blinded independent central review as per the Response Evaluation Criteria in Solid Tumors (version 1.1) in all patients who had measurable disease at baseline and received at least one dose of furmonertinib. Safety was assessed as per the Common Terminology Criteria for Adverse Events (version 4.03) in all patients who received at least one dose of furmonertinib with at least one safety assessment during follow-up. This study is registered with ClinicalTrials.gov (NCT03452592) and is ongoing for survival follow-up. FINDINGS: From Jun 4, 2018, to Dec 8, 2018, 220 patients received furmonertinib treatment. All 220 patients were included in the efficacy and safety analyses. At the data cutoff point of Jan 29, 2020, 71 (32%) patients remained on treatment. The median duration of follow-up was 9·6 months (range 0·7-19·4). The objective response rate was 74% (163 of 220 [95% CI 68-80]). Grade 3 or higher adverse events occurred in 58 (26%) patients and treatment-related grade 3 or higher adverse events occurred in 25 (11%) patients. The most common all-cause grade 3 or higher adverse events were increased γ-glutamyltransferase (five; 2%), increased aspartate aminotransferase, increased alanine aminotransferase, hyponatraemia, hypertension, pulmonary infection, hypermagnesaemia, and pericardial effusion (three each; 1%). Treatment-related diarrhoea was reported in ten (5%) patients and rashes were reported in 16 (7%) patients, all grade 1-2. Serious adverse events were reported in 52 (24%) patients, of which 12 (5%) were possibly treatment-related as evaluated by the investigator. INTERPRETATION:Furmonertinib has promising efficacy and an acceptable safety profile for the treatment of patients with EGFRT790M mutated NSCLC. Furmonertinib is expected to become a new treatment option after first or second generation EGFR TKIs in the Chinese population. FUNDING: Shanghai Allist Pharmaceutical Technology, Ministry of Science and Technology of the People's Republic of China, and Chinese Academy of Medical Sciences. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.
Authors: P Xing; X Zheng; Y Wang; T Chu; S Wang; J Jiang; J Qian; X Han; L Ding; Y Wang; L Cui; H Li; L Li; X Chen; B Han; P Hu; Y Shi Journal: ESMO Open Date: 2022-05-06
Authors: Alyssa Y Li; Karolina Gaebe; Katarzyna J Jerzak; Parneet K Cheema; Arjun Sahgal; Sunit Das Journal: Front Oncol Date: 2022-03-07 Impact factor: 6.244