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 journalArticlepeer-review

21 Citations (Scopus)


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
Publication statusPublished - Feb 1 2017
Externally publishedYes


  • 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


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