PMID- 36805452
OWN - NLM
STAT- MEDLINE
DCOM- 20230329
LR  - 20230519
IS  - 1776-260X (Electronic)
IS  - 1776-2596 (Print)
IS  - 1776-2596 (Linking)
VI  - 18
IP  - 2
DP  - 2023 Mar
TI  - 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.
PG  - 195-207
LID - 10.1007/s11523-023-00946-w [doi]
AB  - 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.
CI  - (c) 2023. The Author(s).
FAU - Hsu, Ping-Chih
AU  - Hsu PC
AD  - Division of Thoracic Medicine, Department of Internal Medicine, Chang Gung 
      Memorial Hospital at Linkou, Taoyuan, 33305, Taiwan.
AD  - Department of Medicine, College of Medicine, Chang Gung University, Taoyuan, 
      33302, Taiwan.
FAU - Lee, Suey-Haur
AU  - Lee SH
AD  - Division of Pulmonary and Critical Care Medicine, Kaohsiung Chang Gung Memorial 
      Hospital, Kaohsiung City, 83301, Taiwan.
FAU - Chiu, Li-Chung
AU  - Chiu LC
AD  - Division of Thoracic Medicine, Department of Internal Medicine, Chang Gung 
      Memorial Hospital at Linkou, Taoyuan, 33305, Taiwan.
AD  - Department of Medicine, College of Medicine, Chang Gung University, Taoyuan, 
      33302, Taiwan.
FAU - Lee, Chung-Shu
AU  - Lee CS
AD  - Division of Thoracic Medicine, Department of Internal Medicine, Chang Gung 
      Memorial Hospital at Linkou, Taoyuan, 33305, Taiwan.
AD  - Department of Thoracic Medicine, New Taipei Municipal TuCheng Hospital, New 
      Taipei, 23652, Taiwan.
FAU - Wu, Chiao-En
AU  - Wu CE
AD  - Department of Medicine, College of Medicine, Chang Gung University, Taoyuan, 
      33302, Taiwan.
AD  - Division of Hematology-Oncology, Department of Internal Medicine, Chang Gung 
      Memorial Hospital at Linkou, Taoyuan, 33305, Taiwan.
FAU - Kuo, Scott Chih-Hsi
AU  - Kuo SC
AD  - Division of Thoracic Medicine, Department of Internal Medicine, Chang Gung 
      Memorial Hospital at Linkou, Taoyuan, 33305, Taiwan.
AD  - Department of Medicine, College of Medicine, Chang Gung University, Taoyuan, 
      33302, Taiwan.
FAU - Ju, Jia-Shiuan
AU  - Ju JS
AD  - Division of Thoracic Medicine, Department of Internal Medicine, Chang Gung 
      Memorial Hospital at Linkou, Taoyuan, 33305, Taiwan.
FAU - Huang, Allen Chung-Cheng
AU  - Huang AC
AD  - Division of Thoracic Medicine, Department of Internal Medicine, Chang Gung 
      Memorial Hospital at Linkou, Taoyuan, 33305, Taiwan.
FAU - Li, Shih-Hong
AU  - Li SH
AD  - Division of Thoracic Medicine, Department of Internal Medicine, Chang Gung 
      Memorial Hospital at Linkou, Taoyuan, 33305, Taiwan.
FAU - Ko, Ho-Wen
AU  - Ko HW
AD  - Division of Thoracic Medicine, Department of Internal Medicine, Chang Gung 
      Memorial Hospital at Linkou, Taoyuan, 33305, Taiwan.
AD  - Department of Medicine, College of Medicine, Chang Gung University, Taoyuan, 
      33302, Taiwan.
FAU - Yang, Cheng-Ta
AU  - Yang CT
AD  - Division of Thoracic Medicine, Department of Internal Medicine, Chang Gung 
      Memorial Hospital at Linkou, Taoyuan, 33305, Taiwan.
AD  - Department of Internal Medicine, Taoyuan Chang Gung Memorial Hospital, Taoyuan, 
      33378, Taiwan.
AD  - Department of Respiratory Therapy, College of Medicine, Chang Gung University, 
      Taoyuan, 33302, Taiwan.
FAU - Wang, Chin-Chou
AU  - Wang CC
AUID- ORCID: 0000-0003-2932-751X
AD  - Department of Medicine, College of Medicine, Chang Gung University, Taoyuan, 
      33302, Taiwan. ccwang5202@yahoo.com.tw.
AD  - Division of Pulmonary and Critical Care Medicine, Kaohsiung Chang Gung Memorial 
      Hospital, Kaohsiung City, 83301, Taiwan. ccwang5202@yahoo.com.tw.
AD  - Department of Thoracic Medicine, New Taipei Municipal TuCheng Hospital, New 
      Taipei, 23652, Taiwan. ccwang5202@yahoo.com.tw.
LA  - eng
PT  - Journal Article
PT  - Multicenter Study
PT  - Observational Study
PT  - Research Support, Non-U.S. Gov't
DEP - 20230220
PL  - France
TA  - Target Oncol
JT  - Targeted oncology
JID - 101270595
RN  - 41UD74L59M (Afatinib)
RN  - 0 (Protein Kinase Inhibitors)
RN  - EC 2.7.10.1 (ErbB Receptors)
RN  - EC 2.7.10.1 (EGFR protein, human)
SB  - IM
MH  - Humans
MH  - Afatinib/pharmacology/therapeutic use
MH  - *Lung Neoplasms/drug therapy/genetics/pathology
MH  - Retrospective Studies
MH  - Taiwan
MH  - Protein Kinase Inhibitors/therapeutic use
MH  - *Adenocarcinoma of Lung/drug therapy/genetics
MH  - ErbB Receptors/genetics/therapeutic use
MH  - Mutation
PMC - PMC10042759
COIS- All authors in this work declare no conflicts of interest.
EDAT- 2023/02/23 06:00
MHDA- 2023/03/29 06:05
PMCR- 2023/02/20
CRDT- 2023/02/22 09:37
PHST- 2023/01/04 00:00 [accepted]
PHST- 2023/03/29 06:05 [medline]
PHST- 2023/02/23 06:00 [pubmed]
PHST- 2023/02/22 09:37 [entrez]
PHST- 2023/02/20 00:00 [pmc-release]
AID - 10.1007/s11523-023-00946-w [pii]
AID - 946 [pii]
AID - 10.1007/s11523-023-00946-w [doi]
PST - ppublish
SO  - Target Oncol. 2023 Mar;18(2):195-207. doi: 10.1007/s11523-023-00946-w. Epub 2023 
      Feb 20.