Clinical characteristics of non-small cell lung cancer patients who experienced acquired resistance during gefitinib treatment

Hye Ryoun Kim, Jae Chol Lee, Young Chul Kim, Kyu Sik Kim, In Jae Oh, Sung Yong Lee, Tae Won Jang, Min Ki Lee, Kyeong Cheol Shin, Gwan Ho Lee, Jeong Seon Ryu, Seung Hoon Jang, Ji Woong Son, Jeong Eun Lee, Sun Young Kim, Hee Joung Kim, Kye Young Lee

Research output: Contribution to journalArticle

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Abstract

Background: The NSCLC patients who experienced good clinical responses to an EGFR-TKI will inevitably develop acquired resistance. A great deal of research is being carried out to discover the molecular mechanisms underlying this resistance. In comparison, few studies have been conducted to find out about the clinical characteristics of acquired resistance in the patients who had responded to an EGFR-TKI. Herein we investigated clinical characteristics of NSCLC patients who experienced acquired resistance during gefitinib therapy. Patients and methods: We reviewed NSCLC patients who showed a clinical benefit from initial gefitinib therapy. All clinical data were obtained from 11 centers of Korean Molecular Lung Cancer Group (KMLCG). The clinical manifestations of acquired resistance, time to progression (TTP), and post-progression survival (PPS) after gefitinib failure were analyzed retrospectively. Results: A total of 417 patients were recruited. Median TTP was 10.2 months (95% CI, 9.5-10.9). TTP showed a significant longer duration in female, non-smoker, and patients with adenocarcinoma. At the time of acquired resistance, 63.3% of the patients showed symptomatic deterioration. Sites of disease progression were as follows: primary lung lesion in 58.4%, previous metastasis in 38.3%, and new metastasis in 54.2%. Patients with EGFR wild type showed a tendency of higher frequency in symptomatic deterioration and newly development of CNS metastasis compared with patients with EGFR mutation. There was a significant difference in newly development of lung metastasis between patients with exon 19 deletion and those with L858R mutation (41.4% vs. 6.3%, p=. 0.02). PPS was 8.9 months (95% CI, 7.4-10.4). Smoking history, PS, new CNS lesion and subsequent chemotherapy were independent factors for PPS. Conclusion: This study suggests that clinical manifestations of acquired resistance may be different according to EGFR mutation status and EGFR mutation genotype. In addition, subsequent chemotherapy confers clinical benefit in terms of PPS in NSCLC patients who experienced acquired resistance after gefitinib therapy.

Original languageEnglish
Pages (from-to)252-258
Number of pages7
JournalLung Cancer
Volume83
Issue number2
DOIs
Publication statusPublished - 2014 Feb 1

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Non-Small Cell Lung Carcinoma
Therapeutics
Neoplasm Metastasis
Mutation
Survival
gefitinib
Drug Therapy
Lung
Disease Progression
Exons
Lung Neoplasms
Adenocarcinoma
Smoking
History
Genotype

Keywords

  • Acquired resistance
  • EGFR-tyrosine kinase inhibitor
  • Failure togefitinib
  • Gefitinib
  • Non-small cell lung cancer
  • Post-progression survival (PPS)

ASJC Scopus subject areas

  • Oncology
  • Pulmonary and Respiratory Medicine
  • Cancer Research

Cite this

Clinical characteristics of non-small cell lung cancer patients who experienced acquired resistance during gefitinib treatment. / Kim, Hye Ryoun; Lee, Jae Chol; Kim, Young Chul; Kim, Kyu Sik; Oh, In Jae; Lee, Sung Yong; Jang, Tae Won; Lee, Min Ki; Shin, Kyeong Cheol; Lee, Gwan Ho; Ryu, Jeong Seon; Jang, Seung Hoon; Son, Ji Woong; Lee, Jeong Eun; Kim, Sun Young; Kim, Hee Joung; Lee, Kye Young.

In: Lung Cancer, Vol. 83, No. 2, 01.02.2014, p. 252-258.

Research output: Contribution to journalArticle

Kim, HR, Lee, JC, Kim, YC, Kim, KS, Oh, IJ, Lee, SY, Jang, TW, Lee, MK, Shin, KC, Lee, GH, Ryu, JS, Jang, SH, Son, JW, Lee, JE, Kim, SY, Kim, HJ & Lee, KY 2014, 'Clinical characteristics of non-small cell lung cancer patients who experienced acquired resistance during gefitinib treatment', Lung Cancer, vol. 83, no. 2, pp. 252-258. https://doi.org/10.1016/j.lungcan.2013.11.008
Kim, Hye Ryoun ; Lee, Jae Chol ; Kim, Young Chul ; Kim, Kyu Sik ; Oh, In Jae ; Lee, Sung Yong ; Jang, Tae Won ; Lee, Min Ki ; Shin, Kyeong Cheol ; Lee, Gwan Ho ; Ryu, Jeong Seon ; Jang, Seung Hoon ; Son, Ji Woong ; Lee, Jeong Eun ; Kim, Sun Young ; Kim, Hee Joung ; Lee, Kye Young. / Clinical characteristics of non-small cell lung cancer patients who experienced acquired resistance during gefitinib treatment. In: Lung Cancer. 2014 ; Vol. 83, No. 2. pp. 252-258.
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T1 - Clinical characteristics of non-small cell lung cancer patients who experienced acquired resistance during gefitinib treatment

AU - Kim, Hye Ryoun

AU - Lee, Jae Chol

AU - Kim, Young Chul

AU - Kim, Kyu Sik

AU - Oh, In Jae

AU - Lee, Sung Yong

AU - Jang, Tae Won

AU - Lee, Min Ki

AU - Shin, Kyeong Cheol

AU - Lee, Gwan Ho

AU - Ryu, Jeong Seon

AU - Jang, Seung Hoon

AU - Son, Ji Woong

AU - Lee, Jeong Eun

AU - Kim, Sun Young

AU - Kim, Hee Joung

AU - Lee, Kye Young

PY - 2014/2/1

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N2 - Background: The NSCLC patients who experienced good clinical responses to an EGFR-TKI will inevitably develop acquired resistance. A great deal of research is being carried out to discover the molecular mechanisms underlying this resistance. In comparison, few studies have been conducted to find out about the clinical characteristics of acquired resistance in the patients who had responded to an EGFR-TKI. Herein we investigated clinical characteristics of NSCLC patients who experienced acquired resistance during gefitinib therapy. Patients and methods: We reviewed NSCLC patients who showed a clinical benefit from initial gefitinib therapy. All clinical data were obtained from 11 centers of Korean Molecular Lung Cancer Group (KMLCG). The clinical manifestations of acquired resistance, time to progression (TTP), and post-progression survival (PPS) after gefitinib failure were analyzed retrospectively. Results: A total of 417 patients were recruited. Median TTP was 10.2 months (95% CI, 9.5-10.9). TTP showed a significant longer duration in female, non-smoker, and patients with adenocarcinoma. At the time of acquired resistance, 63.3% of the patients showed symptomatic deterioration. Sites of disease progression were as follows: primary lung lesion in 58.4%, previous metastasis in 38.3%, and new metastasis in 54.2%. Patients with EGFR wild type showed a tendency of higher frequency in symptomatic deterioration and newly development of CNS metastasis compared with patients with EGFR mutation. There was a significant difference in newly development of lung metastasis between patients with exon 19 deletion and those with L858R mutation (41.4% vs. 6.3%, p=. 0.02). PPS was 8.9 months (95% CI, 7.4-10.4). Smoking history, PS, new CNS lesion and subsequent chemotherapy were independent factors for PPS. Conclusion: This study suggests that clinical manifestations of acquired resistance may be different according to EGFR mutation status and EGFR mutation genotype. In addition, subsequent chemotherapy confers clinical benefit in terms of PPS in NSCLC patients who experienced acquired resistance after gefitinib therapy.

AB - Background: The NSCLC patients who experienced good clinical responses to an EGFR-TKI will inevitably develop acquired resistance. A great deal of research is being carried out to discover the molecular mechanisms underlying this resistance. In comparison, few studies have been conducted to find out about the clinical characteristics of acquired resistance in the patients who had responded to an EGFR-TKI. Herein we investigated clinical characteristics of NSCLC patients who experienced acquired resistance during gefitinib therapy. Patients and methods: We reviewed NSCLC patients who showed a clinical benefit from initial gefitinib therapy. All clinical data were obtained from 11 centers of Korean Molecular Lung Cancer Group (KMLCG). The clinical manifestations of acquired resistance, time to progression (TTP), and post-progression survival (PPS) after gefitinib failure were analyzed retrospectively. Results: A total of 417 patients were recruited. Median TTP was 10.2 months (95% CI, 9.5-10.9). TTP showed a significant longer duration in female, non-smoker, and patients with adenocarcinoma. At the time of acquired resistance, 63.3% of the patients showed symptomatic deterioration. Sites of disease progression were as follows: primary lung lesion in 58.4%, previous metastasis in 38.3%, and new metastasis in 54.2%. Patients with EGFR wild type showed a tendency of higher frequency in symptomatic deterioration and newly development of CNS metastasis compared with patients with EGFR mutation. There was a significant difference in newly development of lung metastasis between patients with exon 19 deletion and those with L858R mutation (41.4% vs. 6.3%, p=. 0.02). PPS was 8.9 months (95% CI, 7.4-10.4). Smoking history, PS, new CNS lesion and subsequent chemotherapy were independent factors for PPS. Conclusion: This study suggests that clinical manifestations of acquired resistance may be different according to EGFR mutation status and EGFR mutation genotype. In addition, subsequent chemotherapy confers clinical benefit in terms of PPS in NSCLC patients who experienced acquired resistance after gefitinib therapy.

KW - Acquired resistance

KW - EGFR-tyrosine kinase inhibitor

KW - Failure togefitinib

KW - Gefitinib

KW - Non-small cell lung cancer

KW - Post-progression survival (PPS)

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