Afatinib in Untreated Stage IIIB/IV Lung Adenocarcinoma with Major Uncommon Epidermal Growth Factor Receptor (EGFR) Mutations (G719X/L861Q/S768I): A Multicenter Observational Study in Taiwan

被引:21
作者
Hsu, Ping-Chih [1 ,2 ]
Lee, Suey-Haur [3 ]
Chiu, Li-Chung [1 ,2 ]
Lee, Chung-Shu [1 ,4 ]
Wu, Chiao-En [2 ,5 ]
Kuo, Scott Chih-Hsi [1 ,2 ]
Ju, Jia-Shiuan [1 ]
Huang, Allen Chung-Cheng [1 ]
Li, Shih-Hong [1 ]
Ko, Ho-Wen [1 ,2 ]
Yang, Cheng-Ta [1 ,6 ,7 ]
Wang, Chin-Chou [2 ,3 ,4 ]
机构
[1] Chang Gung Mem Hosp Linkou, Dept Internal Med, Div Thorac Med, Taoyuan 33305, Taiwan
[2] Chang Gung Univ, Coll Med, Dept Med, Taoyuan 33302, Taiwan
[3] Kaohsiung Chang Gung Mem Hosp, Div Pulm & Crit Care Med, Kaohsiung 83301, Taiwan
[4] New Taipei Municipal TuCheng Hosp, Dept Thorac Med, New Taipei 23652, Taiwan
[5] Chang Gung Mem Hosp Linkou, Dept Internal Med, Div Hematol Oncol, Taoyuan 33305, Taiwan
[6] Taoyuan Chang Gung Mem Hosp, Dept Internal Med, Taoyuan 33378, Taiwan
[7] Chang Gung Univ, Coll Med, Dept Resp Therapy, Taoyuan 33302, Taiwan
关键词
1ST-LINE TREATMENT; OPEN-LABEL; PHASE-III; CANCER; CHEMOTHERAPY; OSIMERTINIB; GEFITINIB; ERLOTINIB; SURVIVAL;
D O I
10.1007/s11523-023-00946-w
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Background Real-world clinical experience with afatinib as a treatment for advanced lung adenocarcinoma harboring uncommon epidermal growth factor receptor (EGFR) mutations (G719X, L861Q and S768I) has rarely been reported. Objective We aimed to perform a retrospective multicenter study to analyze afatinib therapy in untreated advanced lung adenocarcinoma harboring uncommon EGFR mutations. Patients and Methods Between May 2014 and June 2021, the data of 90 stage IIIB/IV lung adenocarcinoma patients with uncommon EGFR mutations (G719X/L861Q/S768I) treated with first-line afatinib from the cancer center database of Linkou, Tucheng, and Kaohsiung Chang Gung Memorial Hospitals were retrospectively retrieved and analyzed. Results Afatinib had an objective response rate (ORR) of 63.3% and a disease control rate (DCR) of 86.7%. The median progression-free survival (PFS) with first-line afatinib therapy was 17.3 months (95% confidence interval (CI), 12.07-22.53), and the median overall survival (OS) was 28.5 months (95% CI, 20.22-36.77) in all study patients. In the multivariate analysis, poor performance (Eastern Cooperative Oncology Group performance status (ECOG PS) >= 2) and brain and liver metastases were independent predictors of unfavorable PFS. The G719X mutation (alone+compound) was an independent predictor of favorable PFS (hazard ratio (HR) = 0.578; 95% CI, 0.355-0.941; P = 0.027). Most afatinib-related adverse events (AEs) were limited to grades 1 and 2 and were manageable. Conclusions First-line afatinib therapy is effective and safe for advanced lung adenocarcinoma harboring uncommon EGFR mutations. The G719X mutation was an independent factor associated with a favorable outcome. Poor performance (ECOG PS >= 2), brain metastasis, and liver metastasis were predictive factors of shorter PFS with first-line afatinib therapy.
引用
收藏
页码:195 / 207
页数:13
相关论文
共 49 条
[1]   UNcommon EGFR Mutations: International Case Series on Efficacy of Osimertinib in Real-Life Practice in First-LiNe Setting (UNICORN) [J].
Bar, Jair ;
Peled, Nir ;
Schokrpur, Shiruyeh ;
Wolner, Mirjana ;
Rotem, Ofer ;
Girard, Nicolas ;
Nana, Frank Aboubakar ;
Derijcke, Sofie ;
Kian, Waleed ;
Patel, Sandip ;
Gantz-Sorotsky, Hadas ;
Zer, Alona ;
Moskovitz, Mor ;
Metro, Giulio ;
Rottenberg, Yakir ;
Calles, Antonio ;
Hochmair, Maximilian ;
Cuppens, Kristof ;
Decoster, Lynn ;
Reck, Martin ;
Limon, Dror ;
Rodriguez, Estelamari ;
Astaras, Christoforos ;
Bettini, Adrienne ;
Hafliger, Simon ;
Addeo, Alfredo .
JOURNAL OF THORACIC ONCOLOGY, 2023, 18 (02) :169-180
[2]   Clinical factors associated with treatment outcomes in EGFR mutant non-small cell lung cancer patients with brain metastases: a case-control observational study [J].
Chen, Yung-Hsuan ;
Chen, Yen-Fu ;
Chen, Chung-Yu ;
Shih, Jin-Yuan ;
Yu, Chong-Jen .
BMC CANCER, 2019, 19 (01)
[3]   Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Treatment Response in Advanced Lung Adenocarcinomas with G719X/L861Q/S768I Mutations [J].
Chiu, Chao-Hua ;
Yang, Cheng-Ta ;
Shih, Jin-Yuan ;
Huang, Ming-Shyan ;
Su, Wu-Chou ;
Lai, Ruay-Sheng ;
Wang, Chin-Chou ;
Hsiao, Shih-Hsin ;
Lin, Yu-Ching ;
Ho, Ching-Liang ;
Hsia, Te-Chun ;
Wu, Ming-Fang ;
Lai, Chun-Liang ;
Lee, Kang-Yun ;
Lin, Chih-Bin ;
Yeh, Diana Yu-Wung ;
Chuang, Chi-Yuan ;
Chang, Fu-Kang ;
Tsai, Chun-Ming ;
Perng, Reury-Perng ;
Yang, James Chih-Hsin .
JOURNAL OF THORACIC ONCOLOGY, 2015, 10 (05) :793-799
[4]   Osimertinib for Patients With Non-Small-Cell Lung Cancer Harboring Uncommon EGFR Mutations: A Multicenter, Open-Label, Phase II Trial (KCSG-LU15-09) [J].
Cho, Jang Ho ;
Lim, Sung Hee ;
An, Ho Jung ;
Kim, Ki Hwan ;
Park, Keon Uk ;
Kang, Eun Joo ;
Choi, Yoon Hee ;
Ahn, Mi Sun ;
Lee, Myung Hee ;
Sun, Jong-Mu ;
Lee, Se-Hoon ;
Ahn, Jin Seok ;
Park, Keunchil ;
Ahn, Myung-Ju .
JOURNAL OF CLINICAL ONCOLOGY, 2020, 38 (05)
[5]   EGFR/c-Met and mTOR signaling are predictors of survival in non-small cell lung cancer [J].
Crees, Zachary D. ;
Shearrow, Caleb ;
Lin, Leo ;
Girard, Jennifer ;
Arasi, Kavin ;
Bhoraskar, Aayush ;
Berei, Joseph ;
Eckburg, Adam ;
Anderson, Austin D. ;
Garcia, Christian ;
Munger, Ariana ;
Palani, Sunil ;
Smith, Thomas J. ;
Sreenivassappa, Shylendra B. ;
Vitali, Connie ;
David, Odile ;
Puri, Neelu .
THERAPEUTIC ADVANCES IN MEDICAL ONCOLOGY, 2020, 12
[6]   Bevacizumab Reduces S100A9-Positive MDSCs Linked to Intracranial Control in Patients with EGFR-Mutant Lung Adenocarcinoma [J].
Feng, Po-Hao ;
Chen, Kuan-Yuan ;
Huang, Yu-Chen ;
Luo, Ching-Shan ;
Wu, Shen Ming ;
Chen, Tzu-Tao ;
Lee, Chun-Nin ;
Yeh, Chi-Tai ;
Chuang, Hsiao-Chi ;
Han, Chia-Li ;
Lin, Chiou-Feng ;
Lee, Wei-Hwa ;
Kuo, Chih-Hsi ;
Lee, Kang-Yun .
JOURNAL OF THORACIC ONCOLOGY, 2018, 13 (07) :958-967
[7]  
Hsu PC., 2016, Cancer Treat Res Commun, V9, P48, DOI [10.1016/j.ctarc.2016.07.005, DOI 10.1016/J.CTARC.2016.07.005]
[8]   First- or second-generation epidermal growth factor receptor tyrosine kinase inhibitors in a large, real-world cohort of patients with non-small cell lung cancer [J].
Huang, Allen Chung-Cheng ;
Huang, Chi-Hsien ;
Ju, Jia-Shiuan ;
Chiu, Tzu-Hsuan ;
Tung, Pi-Hung ;
Wang, Chin-Chou ;
Liu, Chien-Ying ;
Chung, Fu-Tsai ;
Fang, Yueh-Fu ;
Guo, Yi-Ke ;
Kuo, Chih-Hsi Scott ;
Yang, Cheng-Ta .
THERAPEUTIC ADVANCES IN MEDICAL ONCOLOGY, 2021, 13
[9]   The relative importance of predictive factors for single first-generation EGFR-TKI use for more than 5 years in patients with advanced non-small cell lung cancer: Taiwan multicenter TIPS-5 study [J].
Huang, Yen-Hsiang ;
Hung, Jen-Yu ;
Ko, How-Wen ;
Su, Po-Lan ;
Lai, Chun-Liang ;
Chang, Huang-Chih ;
Hsia, Te-Chun ;
Lin, Sheng-Hao ;
Wu, Kuan-Li ;
Yang, Cheng-Ta ;
Su, Wu-Chou ;
Chu, Yi-Chun ;
Wang, Chin-Chou ;
Liao, Wei-Yu ;
Lin, Yen-Ting ;
Lin, Ching-Hsiung ;
Lin, Meng-Chih ;
Hsu, Kuo-Hsuan ;
Tseng, Jeng-Sen ;
Yang, Tsung-Ying ;
Chen, Kun-Chieh ;
Lee, Mei-Hsuan ;
Yu, Sung-Liang ;
Ho, Chao-Chi ;
Chang, Gee-Chen .
THERAPEUTIC ADVANCES IN MEDICAL ONCOLOGY, 2021, 13
[10]   First-line Afatinib in Patients With Non-small-cell Lung Cancer With Uncommon EGFR Mutations in South Korea [J].
Kim, Mi-Hyun ;
Choi, Chang Min ;
Lee, Sung Yong ;
Park, Cheol Kyu ;
Chang, Yoon Soo ;
Lee, Kye Young ;
Kim, Seung Joon ;
Yang, Sei Hoon ;
Ryu, Jeong Seon ;
Lee, Jeong Eun ;
Lee, Shin Yup ;
Park, Chan Kwon ;
Lee, Sang Hoon ;
Jang, Seung Hun ;
Yoon, Seong Hoon ;
Jang, Tae Won .
ANTICANCER RESEARCH, 2022, 42 (03) :1615-1622