Cancer Res Treat.  2018 Oct;50(4):1164-1174. 10.4143/crt.2017.460.

Intercalated Treatment Following Rebiopsy Is Associated with a Shorter Progression-Free Survival of Osimertinib Treatment

  • 1Division of Chest Medicine, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan.
  • 2Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan.
  • 3Institute of Biomedical Sciences, National Chung Hsing University, Taichung, Taiwan.
  • 4Division of Critical Care and Respiratory Therapy, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan.
  • 5Department of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan University, Taipei, Taiwan.
  • 6Department of Laboratory Medicine, National Taiwan University Hospital, Taipei, Taiwan.
  • 7Center of Genomic Medicine, National Taiwan University College of Medicine, Taipei, Taiwan.
  • 8Department of Pathology and Graduate Institute of Pathology, National Taiwan University College of Medicine, Taipei, Taiwan.
  • 9Center for Optoelectronic Biomedicine, National Taiwan University College of Medicine, Taipei, Taiwan.
  • 10Comprehensive Cancer Center, Taichung Veterans General Hospital, Taichung, Taiwan.


Epidermal growth factor receptor (EGFR) T790M mutation serves as an important predictor of osimertinib efficacy. However, little is known about how it works among patients with various timings of T790M emergence and treatment.
Advanced EGFR-mutant lung adenocarcinoma patients with positive T790M mutation in tumor were retrospectively enrolled and observed to determine the outcomes of osimertinib treatment. We evaluated the association between patients' characteristics and the efficacy of osimertinib treatment, particularly with respect to the timing of T790M emergence and osimertinib prescription.
A total of 91 patients were enrolled, including 14 (15.4%) with primary and 77 (84.6%) with acquired T790M mutation. The objective response rate and disease controlratewere 60.9% and 85.1%, respectively. The median progression-free survival (PFS) and overall survival were 11.5 months (95% confidence interval [CI], 9.0 to 14.0) and 30.4 months (95% CI, 11.3 to 49.5), respectively. There was no significant difference in response rate and PFS between primary and acquired T790M populations. In the acquired T790M subgroup, patientswho received osimertinib after T790M had been confirmed by rebiopsy had a longer PFS than those with intercalated treatments between rebiopsy and osimertinib prescription (14.0 months [95% CI, 9.0 to 18.9] vs. 7.2 months [95% CI, 3.7 to 10.8]; adjusted hazard ratio, 0.48 [95% CI, 0.24 to 0.98; p=0.043]). Rebiopsy timing did not influence the outcome.
Osimertinib prescription with intercalated treatment following rebiopsy but not the timing of T790M emergence influenced the treatment outcome. We suggest that it is better to start osimertinib treatment once T790M mutation has been confirmed by biopsy.


Epidermal growth factor receptor; Lung adenocarcinoma; Osimertinib

MeSH Terms

Disease-Free Survival*
Receptor, Epidermal Growth Factor
Retrospective Studies
Treatment Outcome
Receptor, Epidermal Growth Factor


  • Fig. 1. Patient selection flowchart. EGFR, epidermal growth factor receptor; TKI, tyrosine kinase inhibitor; PD, disease progression.

  • Fig. 2. Kaplan-Meier plot showing progression-free survival of patients with acquired T790M in relation to rebiopsy timing (p-value by log-rank test). EGFR, epidermal growth factor receptor; TKI, tyrosine kinase inhibitor; PD, disease progression; CI, confidence interval.

  • Fig. 3. Kaplan-Meier plot showing progression-free survival of patients with acquired T790M in relation to osimertinib treatment timing (p-value by log-rank test). CI, confidence interval.



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