Liver metastasis predicts poorer prognosis in stage IV lung adenocarcinoma patients receiving first-line gefitinib.
OBJECTIVE
Gefitinib is currently used as a first-line therapy in patients of advanced non-small cell lung cancer (NSCLC) with susceptible epidermal growth factor receptor (EGFR) mutations. However, treatment outcomes of these patients vary. This study was conducted to evaluate the impact of specific metastatic sites on treatment outcomes of patients with stage IV lung adenocarcinoma with susceptible EGFR mutations receiving first-line gefitinib, focusing on the impact of liver metastasis.


METHODS
Between October 2009 and April 2014, patients of stage IV lung adenocarcinoma harboring EGFR mutation in exon 19 or 21, who received first-line gefitinib treatment, were enrolled in two hospitals and followed until December 22, 2014. The impacts of various clinical features, including sex, age, smoking history, performance status, EGFR mutation site, metastatic sites, etc., on progression-free survival (PFS) and overall survival (OS) were analyzed.


RESULTS
A total of 148 patients were eligible for analysis. Patients with liver metastasis on initial diagnosis (n=19) had shorter PFS and OS than those without liver metastasis did (median of PFS, 6.7 vs. 11.2 months, p<0.0001; median of OS, 9.2 vs. 17.5 months, p<0.0001). Multivariable Cox regression analysis showed liver metastasis was an independent poor prognostic factor for PFS (HR=2.939 [95% CI: 1.729-4.997], p<0.0001) and OS (HR=3.300 [95% CI: 1.708-6.373], p=0.0004).


CONCLUSIONS
Liver metastasis predicts poorer PFS and OS in stage IV lung adenocarcinoma patients with susceptible gene mutations receiving first-line gefitinib. Further study is warranted to elucidate the underlying mechanisms and find treatment modalities to improve prognosis of these patients.
Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Kaohsiung Medical University Hospital, No. 100, Tz-You 1st Road, 807 Kaohsiung, Taiwan; Department of Internal Medicine, Pingtung Hospital, Ministry of Health and Welfare, Pingtung, Taiwan.
Kuan-Li
KL
Wu
Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Kaohsiung Medical University Hospital, No. 100, Tz-You 1st Road, 807 Kaohsiung, Taiwan; Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
Ming-Ju
MJ
Tsai
Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Kaohsiung Medical University Hospital, No. 100, Tz-You 1st Road, 807 Kaohsiung, Taiwan; Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Internal Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung, Taiwan; Department of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
Chih-Jen
CJ
Yang
Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Kaohsiung Medical University Hospital, No. 100, Tz-You 1st Road, 807 Kaohsiung, Taiwan; Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
Wei-An
WA
Chang
Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Kaohsiung Medical University Hospital, No. 100, Tz-You 1st Road, 807 Kaohsiung, Taiwan; Department of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
Jen-Yu
JY
Hung
Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Kaohsiung Medical University Hospital, No. 100, Tz-You 1st Road, 807 Kaohsiung, Taiwan; Department of Nursing, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
Chun-Ju
CJ
Yen
Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Kaohsiung Medical University Hospital, No. 100, Tz-You 1st Road, 807 Kaohsiung, Taiwan; Department of Nursing, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
Chi-Hsiang
CH
Shen
Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Kaohsiung Medical University Hospital, No. 100, Tz-You 1st Road, 807 Kaohsiung, Taiwan.
Tzu-Yu
TY
Kuo
Division of Chest Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
Jui-Ying
JY
Lee
Division of Chest Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Respiratory Care, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
Shah-Hwa
SH
Chou
Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Division of Hematology and Oncology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
Ta-Chih
TC
Liu
Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Kaohsiung Medical University Hospital, No. 100, Tz-You 1st Road, 807 Kaohsiung, Taiwan; Department of Respiratory Care, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
Inn-Wen
IW
Chong
Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Kaohsiung Medical University Hospital, No. 100, Tz-You 1st Road, 807 Kaohsiung, Taiwan; Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan. Electronic address: shyang@kmu.edu.tw.
Ming-Shyan
MS
Huang
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology*; D000077192:Adenocarcinoma of Lung; D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000473:pathology; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D005260:Female; D000077156:Gefitinib; D006801:Humans; D008113:Liver Neoplasms / Q000473:pathology* / Q000556:secondary*; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000187:drug effects; D009367:Neoplasm Staging / Q000379:methods; D011379:Prognosis; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011799:Quinazolines / Q000627:therapeutic use*; D012189:Retrospective Studies; D016896:Treatment Outcome
D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D066246:ErbB Receptors; D000077156:Gefitinib
Adenocarcinoma; Epidermal growth factor receptor tyrosine kinase inhibitor; Gefitinib; Liver metastasis; Lung cancer