Predictive factors for EGFR-tyrosine kinase inhibitor retreatment in patients with EGFR-mutated non-small-cell lung cancer – A multicenter retrospective SEQUENCE study

Gee Chen Chang, Chien Hua Tseng, Kuo Hsuan Hsu, Chong Jen Yu, Cheng Ta Yang, Kun Chieh Chen, Tsung Ying Yang, Jeng Sen Tseng, Chien Ying Liu, Wei Yu Liao, Te Chun Hsia, Chih Yen Tu, Meng Chih Lin, Ying Huang Tsai, Meng Jer Hsieh, Wen Shuo Wu, Yuh Min Chen

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Background Acquired resistance occurs in most non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutations experiencing a response to EGFR-tyrosine kinase inhibitor (TKI) initially. We investigated EGFR-TKI retreatment in patients who had previously received EGFR-TKI followed by chemotherapy. Materials and methods This was a retrospective multicenter study. Patients with locally advanced or metastatic adenocarcinoma or TTF-1 (+) NSCLC, positive EGFR sensitive mutation, and EGFR-TKI reuse after initial EGFR-TKI followed by chemotherapy were enrolled. The objectives were to assess the objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS) of EGFR TKI switched retreatment. Results In total, 205 patients were enrolled, with a median age of 61.8 years (range 31.4–92.9). There was a larger proportion of females (62.9%) than males, and more never-smokers (73.2%) than ever-smokers. In the initial EGFR-TKI administration, 57.6% of patients showed a complete response (CR) or partial response (PR), and 34.6% had stable disease (SD); in the second-line chemotherapy, 13.7% had PR, and 58.0% had SD; in the EGFR-TKI retreatment, 7.3% had PR, and 37.1% had SD. The median PFS of first-line EGFR-TKI was 8.0 months (95% CI 7.3–8.2), and retreatment EGFR-TKI was 4.1 months (95% CI 2.7–4.6). The median OS since the start of the first-line EGFR-TKI therapy was 35.9 months (95% CI 28.8–50.9), and since the start of EGFR-TKI retreatment was 12.6 months (95% CI 10.4–20.9). In the univariable and multivariable regression analysis of factors associated with PFS of EGFR-TKI retreatment, time interval between the two EGFR TKIs equal to or more than 7 months was statistically significant (HR = 0.62, 95% CI 0.44-0.86; HR = 0.6, 95% CI 0.43–0.86), both p < 0.01. Females with exon 21 mutation also showed a significant difference between the two groups (HR = 0.51, 95% CI 0.30–0.86; HR = 0.52 (0.31–0.88), both p < 0.05). Conclusions EGFR-TKI retreatment was effective in prolonging survival, and was shown to be a worthwhile option for EGFR-mutated NSCLC patients after failure of first-line EGFR-TKI and chemotherapy. The survival benefit was especially pronounced in patients with longer drug holidays from the initial EGFR-TKI and in females with the exon 21 mutation.

Original languageEnglish
Pages (from-to)58-64
Number of pages7
JournalLung Cancer
Volume104
DOIs
Publication statusPublished - Feb 1 2017
Externally publishedYes

Fingerprint

Retreatment
Epidermal Growth Factor Receptor
Non-Small Cell Lung Carcinoma
Protein-Tyrosine Kinases
Retrospective Studies
Disease-Free Survival
Drug Therapy
Mutation
Survival
Exons
Holidays

Keywords

  • Adenocarcinoma
  • Drug holiday
  • EGFR mutation
  • EGFR TKI retreatment
  • Exon 21 mutation
  • Females
  • Lung cancer
  • Overall survival
  • Progression free survival

ASJC Scopus subject areas

  • Oncology
  • Pulmonary and Respiratory Medicine
  • Cancer Research

Cite this

Predictive factors for EGFR-tyrosine kinase inhibitor retreatment in patients with EGFR-mutated non-small-cell lung cancer – A multicenter retrospective SEQUENCE study. / Chang, Gee Chen; Tseng, Chien Hua; Hsu, Kuo Hsuan; Yu, Chong Jen; Yang, Cheng Ta; Chen, Kun Chieh; Yang, Tsung Ying; Tseng, Jeng Sen; Liu, Chien Ying; Liao, Wei Yu; Hsia, Te Chun; Tu, Chih Yen; Lin, Meng Chih; Tsai, Ying Huang; Hsieh, Meng Jer; Wu, Wen Shuo; Chen, Yuh Min.

In: Lung Cancer, Vol. 104, 01.02.2017, p. 58-64.

Research output: Contribution to journalArticle

Chang, GC, Tseng, CH, Hsu, KH, Yu, CJ, Yang, CT, Chen, KC, Yang, TY, Tseng, JS, Liu, CY, Liao, WY, Hsia, TC, Tu, CY, Lin, MC, Tsai, YH, Hsieh, MJ, Wu, WS & Chen, YM 2017, 'Predictive factors for EGFR-tyrosine kinase inhibitor retreatment in patients with EGFR-mutated non-small-cell lung cancer – A multicenter retrospective SEQUENCE study', Lung Cancer, vol. 104, pp. 58-64. https://doi.org/10.1016/j.lungcan.2016.12.002
Chang, Gee Chen ; Tseng, Chien Hua ; Hsu, Kuo Hsuan ; Yu, Chong Jen ; Yang, Cheng Ta ; Chen, Kun Chieh ; Yang, Tsung Ying ; Tseng, Jeng Sen ; Liu, Chien Ying ; Liao, Wei Yu ; Hsia, Te Chun ; Tu, Chih Yen ; Lin, Meng Chih ; Tsai, Ying Huang ; Hsieh, Meng Jer ; Wu, Wen Shuo ; Chen, Yuh Min. / Predictive factors for EGFR-tyrosine kinase inhibitor retreatment in patients with EGFR-mutated non-small-cell lung cancer – A multicenter retrospective SEQUENCE study. In: Lung Cancer. 2017 ; Vol. 104. pp. 58-64.
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abstract = "Background Acquired resistance occurs in most non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutations experiencing a response to EGFR-tyrosine kinase inhibitor (TKI) initially. We investigated EGFR-TKI retreatment in patients who had previously received EGFR-TKI followed by chemotherapy. Materials and methods This was a retrospective multicenter study. Patients with locally advanced or metastatic adenocarcinoma or TTF-1 (+) NSCLC, positive EGFR sensitive mutation, and EGFR-TKI reuse after initial EGFR-TKI followed by chemotherapy were enrolled. The objectives were to assess the objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS) of EGFR TKI switched retreatment. Results In total, 205 patients were enrolled, with a median age of 61.8 years (range 31.4–92.9). There was a larger proportion of females (62.9{\%}) than males, and more never-smokers (73.2{\%}) than ever-smokers. In the initial EGFR-TKI administration, 57.6{\%} of patients showed a complete response (CR) or partial response (PR), and 34.6{\%} had stable disease (SD); in the second-line chemotherapy, 13.7{\%} had PR, and 58.0{\%} had SD; in the EGFR-TKI retreatment, 7.3{\%} had PR, and 37.1{\%} had SD. The median PFS of first-line EGFR-TKI was 8.0 months (95{\%} CI 7.3–8.2), and retreatment EGFR-TKI was 4.1 months (95{\%} CI 2.7–4.6). The median OS since the start of the first-line EGFR-TKI therapy was 35.9 months (95{\%} CI 28.8–50.9), and since the start of EGFR-TKI retreatment was 12.6 months (95{\%} CI 10.4–20.9). In the univariable and multivariable regression analysis of factors associated with PFS of EGFR-TKI retreatment, time interval between the two EGFR TKIs equal to or more than 7 months was statistically significant (HR = 0.62, 95{\%} CI 0.44-0.86; HR = 0.6, 95{\%} CI 0.43–0.86), both p < 0.01. Females with exon 21 mutation also showed a significant difference between the two groups (HR = 0.51, 95{\%} CI 0.30–0.86; HR = 0.52 (0.31–0.88), both p < 0.05). Conclusions EGFR-TKI retreatment was effective in prolonging survival, and was shown to be a worthwhile option for EGFR-mutated NSCLC patients after failure of first-line EGFR-TKI and chemotherapy. The survival benefit was especially pronounced in patients with longer drug holidays from the initial EGFR-TKI and in females with the exon 21 mutation.",
keywords = "Adenocarcinoma, Drug holiday, EGFR mutation, EGFR TKI retreatment, Exon 21 mutation, Females, Lung cancer, Overall survival, Progression free survival",
author = "Chang, {Gee Chen} and Tseng, {Chien Hua} and Hsu, {Kuo Hsuan} and Yu, {Chong Jen} and Yang, {Cheng Ta} and Chen, {Kun Chieh} and Yang, {Tsung Ying} and Tseng, {Jeng Sen} and Liu, {Chien Ying} and Liao, {Wei Yu} and Hsia, {Te Chun} and Tu, {Chih Yen} and Lin, {Meng Chih} and Tsai, {Ying Huang} and Hsieh, {Meng Jer} and Wu, {Wen Shuo} and Chen, {Yuh Min}",
year = "2017",
month = "2",
day = "1",
doi = "10.1016/j.lungcan.2016.12.002",
language = "English",
volume = "104",
pages = "58--64",
journal = "Lung Cancer",
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TY - JOUR

T1 - Predictive factors for EGFR-tyrosine kinase inhibitor retreatment in patients with EGFR-mutated non-small-cell lung cancer – A multicenter retrospective SEQUENCE study

AU - Chang, Gee Chen

AU - Tseng, Chien Hua

AU - Hsu, Kuo Hsuan

AU - Yu, Chong Jen

AU - Yang, Cheng Ta

AU - Chen, Kun Chieh

AU - Yang, Tsung Ying

AU - Tseng, Jeng Sen

AU - Liu, Chien Ying

AU - Liao, Wei Yu

AU - Hsia, Te Chun

AU - Tu, Chih Yen

AU - Lin, Meng Chih

AU - Tsai, Ying Huang

AU - Hsieh, Meng Jer

AU - Wu, Wen Shuo

AU - Chen, Yuh Min

PY - 2017/2/1

Y1 - 2017/2/1

N2 - Background Acquired resistance occurs in most non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutations experiencing a response to EGFR-tyrosine kinase inhibitor (TKI) initially. We investigated EGFR-TKI retreatment in patients who had previously received EGFR-TKI followed by chemotherapy. Materials and methods This was a retrospective multicenter study. Patients with locally advanced or metastatic adenocarcinoma or TTF-1 (+) NSCLC, positive EGFR sensitive mutation, and EGFR-TKI reuse after initial EGFR-TKI followed by chemotherapy were enrolled. The objectives were to assess the objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS) of EGFR TKI switched retreatment. Results In total, 205 patients were enrolled, with a median age of 61.8 years (range 31.4–92.9). There was a larger proportion of females (62.9%) than males, and more never-smokers (73.2%) than ever-smokers. In the initial EGFR-TKI administration, 57.6% of patients showed a complete response (CR) or partial response (PR), and 34.6% had stable disease (SD); in the second-line chemotherapy, 13.7% had PR, and 58.0% had SD; in the EGFR-TKI retreatment, 7.3% had PR, and 37.1% had SD. The median PFS of first-line EGFR-TKI was 8.0 months (95% CI 7.3–8.2), and retreatment EGFR-TKI was 4.1 months (95% CI 2.7–4.6). The median OS since the start of the first-line EGFR-TKI therapy was 35.9 months (95% CI 28.8–50.9), and since the start of EGFR-TKI retreatment was 12.6 months (95% CI 10.4–20.9). In the univariable and multivariable regression analysis of factors associated with PFS of EGFR-TKI retreatment, time interval between the two EGFR TKIs equal to or more than 7 months was statistically significant (HR = 0.62, 95% CI 0.44-0.86; HR = 0.6, 95% CI 0.43–0.86), both p < 0.01. Females with exon 21 mutation also showed a significant difference between the two groups (HR = 0.51, 95% CI 0.30–0.86; HR = 0.52 (0.31–0.88), both p < 0.05). Conclusions EGFR-TKI retreatment was effective in prolonging survival, and was shown to be a worthwhile option for EGFR-mutated NSCLC patients after failure of first-line EGFR-TKI and chemotherapy. The survival benefit was especially pronounced in patients with longer drug holidays from the initial EGFR-TKI and in females with the exon 21 mutation.

AB - Background Acquired resistance occurs in most non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutations experiencing a response to EGFR-tyrosine kinase inhibitor (TKI) initially. We investigated EGFR-TKI retreatment in patients who had previously received EGFR-TKI followed by chemotherapy. Materials and methods This was a retrospective multicenter study. Patients with locally advanced or metastatic adenocarcinoma or TTF-1 (+) NSCLC, positive EGFR sensitive mutation, and EGFR-TKI reuse after initial EGFR-TKI followed by chemotherapy were enrolled. The objectives were to assess the objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS) of EGFR TKI switched retreatment. Results In total, 205 patients were enrolled, with a median age of 61.8 years (range 31.4–92.9). There was a larger proportion of females (62.9%) than males, and more never-smokers (73.2%) than ever-smokers. In the initial EGFR-TKI administration, 57.6% of patients showed a complete response (CR) or partial response (PR), and 34.6% had stable disease (SD); in the second-line chemotherapy, 13.7% had PR, and 58.0% had SD; in the EGFR-TKI retreatment, 7.3% had PR, and 37.1% had SD. The median PFS of first-line EGFR-TKI was 8.0 months (95% CI 7.3–8.2), and retreatment EGFR-TKI was 4.1 months (95% CI 2.7–4.6). The median OS since the start of the first-line EGFR-TKI therapy was 35.9 months (95% CI 28.8–50.9), and since the start of EGFR-TKI retreatment was 12.6 months (95% CI 10.4–20.9). In the univariable and multivariable regression analysis of factors associated with PFS of EGFR-TKI retreatment, time interval between the two EGFR TKIs equal to or more than 7 months was statistically significant (HR = 0.62, 95% CI 0.44-0.86; HR = 0.6, 95% CI 0.43–0.86), both p < 0.01. Females with exon 21 mutation also showed a significant difference between the two groups (HR = 0.51, 95% CI 0.30–0.86; HR = 0.52 (0.31–0.88), both p < 0.05). Conclusions EGFR-TKI retreatment was effective in prolonging survival, and was shown to be a worthwhile option for EGFR-mutated NSCLC patients after failure of first-line EGFR-TKI and chemotherapy. The survival benefit was especially pronounced in patients with longer drug holidays from the initial EGFR-TKI and in females with the exon 21 mutation.

KW - Adenocarcinoma

KW - Drug holiday

KW - EGFR mutation

KW - EGFR TKI retreatment

KW - Exon 21 mutation

KW - Females

KW - Lung cancer

KW - Overall survival

KW - Progression free survival

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DO - 10.1016/j.lungcan.2016.12.002

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C2 - 28213001

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JO - Lung Cancer

JF - Lung Cancer

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