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

Dong Wan Kim, Se Hoon Lee, Jong Seok Lee, Myung Ah Lee, Jin Hyoung Kang, Si Young Kim, Sang Won Shin, Hoon Kyo Kim, Dae Seog Heo

Research output: Contribution to journalArticle

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Abstract

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-naïve 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).

Original languageEnglish
Pages (from-to)65-69
Number of pages5
JournalLung Cancer
Volume71
Issue number1
DOIs
Publication statusPublished - 2011 Jan 1

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Epidermal Growth Factor Receptor
Safety
Mutation
Exons
Therapeutics
Disease-Free Survival
Survival
gefitinib
Adenocarcinoma of lung
Neoplasms
Sequence Deletion
Insertional Mutagenesis
Point Mutation
Disease Progression
Survival Rate

Keywords

  • Adenocarcinoma
  • Cancer
  • Chemotherapy.
  • EGFR
  • Gefitinib
  • Lung
  • Mutations

ASJC Scopus subject areas

  • Oncology
  • Pulmonary and Respiratory Medicine
  • Cancer Research

Cite this

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. / Kim, Dong Wan; Lee, Se Hoon; Lee, Jong Seok; Lee, Myung Ah; Kang, Jin Hyoung; Kim, Si Young; Shin, Sang Won; Kim, Hoon Kyo; Heo, Dae Seog.

In: Lung Cancer, Vol. 71, No. 1, 01.01.2011, p. 65-69.

Research output: Contribution to journalArticle

Kim, Dong Wan ; Lee, Se Hoon ; Lee, Jong Seok ; Lee, Myung Ah ; Kang, Jin Hyoung ; Kim, Si Young ; Shin, Sang Won ; Kim, Hoon Kyo ; Heo, Dae Seog. / 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. In: Lung Cancer. 2011 ; Vol. 71, No. 1. pp. 65-69.
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T1 - 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

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AU - Lee, Jong Seok

AU - Lee, Myung Ah

AU - Kang, Jin Hyoung

AU - Kim, Si Young

AU - Shin, Sang Won

AU - Kim, Hoon Kyo

AU - Heo, Dae Seog

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N2 - 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-naïve 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).

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KW - Cancer

KW - Chemotherapy.

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KW - Gefitinib

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KW - Mutations

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