PMID- 20430469
OWN - NLM
STAT- MEDLINE
DCOM- 20110328
LR  - 20220311
IS  - 1872-8332 (Electronic)
IS  - 0169-5002 (Linking)
VI  - 71
IP  - 1
DP  - 2011 Jan
TI  - A multicenter phase II study to evaluate the efficacy and safety of gefitinib as 
      first-line treatment for Korean patients with advanced pulmonary adenocarcinoma 
      harboring EGFR mutations.
PG  - 65-9
LID - 10.1016/j.lungcan.2010.04.005 [doi]
AB  - This study was designed to prospectively evaluate the efficacy and safety of 
      first-line gefitinib treatment in patients with advanced pulmonary adenocarcinoma 
      harboring epidermal growth factor receptor (EGFR) mutations and to explore the 
      molecular factors affecting the efficacy of gefitinib. Tumor tissue, derived from 
      either the original tumor or the metastatic or recurrent site was taken from 
      chemo-naive pts with advanced (stage IIIB, IV, and recurrent) pulmonary 
      adenocarcinoma. Tumor genomic DNA underwent direct sequencing for EGFR exons 18, 
      19, 20, and 21. Patients with EGFR mutations received 250 mg of gefitinib daily 
      until disease progression or unacceptable toxicity. The primary endpoint was 
      objective response rate (ORR). Secondary endpoints were progression free survival 
      (PFS), overall survival (OS) and tolerability. Out of 147 screened patients, 45 
      pts (31%) had EGFR mutations and received gefitinib. The most common EGFR 
      mutations were in-frame exon 19 deletions (29 pts, 64%) and L858R point mutation 
      in exon 21 (15 pts, 33%). One patient had atypical mutation of L861Q in exon 21. 
      The ORR was 53.3% (95% CI, 38.6-67.9) and disease control rate (DCR) including 
      stable disease was 86.7%. The median progression free survival (PFS) was 398 days 
      and the median overall survival (OS) was 819 days. Treatment was well tolerated. 
      Grade 3/4 adverse events (AEs) were reported by 6 patients and treatment-related 
      Grade 3 AEs by 3 patients. There were no treatment-related Grade 4 AEs. 
      Exploratory subgroup analysis according to the EGFR mutation subtypes was carried 
      out. The ORR and DCR were higher in patients with exon 19 deletions than those 
      with L858R (62.1% vs 33.3%; P=0.0705 and 96.6% vs 66.7%; P=0.0062, respectively). 
      All 4 patients with progressive disease had a L858R mutation. No secondary 
      resistant mutations such as T790M mutation or insertions in exon 20 were found in 
      those patients. In addition, OS was significantly better in patients with exon 19 
      deletions than those with L858R (24-month OS rate was 72.1% vs 32.0%, P=0.0148). 
      Gefitinib as the first-line treatment for Korean patients with advanced pulmonary 
      adenocarcinoma harboring EGFR mutations was effective and well tolerated. 
      Subgroup analysis suggests that the benefit from gefitinib treatment was more 
      prominent in patients with the exon 19 deletion mutations (ClinicalTrials.gov 
      number, NCT00344773).
CI  - Copyright (c) 2010 Elsevier Ireland Ltd. All rights reserved.
FAU - Kim, Dong-Wan
AU  - Kim DW
AD  - Department of Internal Medicine, Seoul National University Hospital, Seoul, 
      Republic of Korea.
FAU - Lee, Se-Hoon
AU  - Lee SH
FAU - Lee, Jong Seok
AU  - Lee JS
FAU - Lee, Myung Ah
AU  - Lee MA
FAU - Kang, Jin Hyoung
AU  - Kang JH
FAU - Kim, Si Young
AU  - Kim SY
FAU - Shin, Sang Won
AU  - Shin SW
FAU - Kim, Hoon-Kyo
AU  - Kim HK
FAU - Heo, Dae Seog
AU  - Heo DS
LA  - eng
SI  - ClinicalTrials.gov/NCT00344773
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, Non-U.S. Gov't
PL  - Ireland
TA  - Lung Cancer
JT  - Lung cancer (Amsterdam, Netherlands)
JID - 8800805
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 0 (Quinazolines)
RN  - EC 2.7.10.1 (ErbB Receptors)
RN  - S65743JHBS (Gefitinib)
SB  - IM
MH  - Adenocarcinoma/*drug therapy/enzymology/genetics
MH  - Antineoplastic Agents/therapeutic use
MH  - Disease-Free Survival
MH  - ErbB Receptors/*genetics
MH  - Female
MH  - Gefitinib
MH  - Humans
MH  - Lung Neoplasms/*drug therapy/enzymology/genetics
MH  - Male
MH  - Middle Aged
MH  - *Mutation
MH  - Prospective Studies
MH  - Protein Kinase Inhibitors/therapeutic use
MH  - Quinazolines/*therapeutic use
EDAT- 2010/05/01 06:00
MHDA- 2011/03/29 06:00
CRDT- 2010/05/01 06:00
PHST- 2010/01/19 00:00 [received]
PHST- 2010/03/07 00:00 [revised]
PHST- 2010/04/01 00:00 [accepted]
PHST- 2010/05/01 06:00 [entrez]
PHST- 2010/05/01 06:00 [pubmed]
PHST- 2011/03/29 06:00 [medline]
AID - S0169-5002(10)00164-9 [pii]
AID - 10.1016/j.lungcan.2010.04.005 [doi]
PST - ppublish
SO  - Lung Cancer. 2011 Jan;71(1):65-9. doi: 10.1016/j.lungcan.2010.04.005.