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Mutation abundance affects the efficacy of EGFR tyrosine kinase inhibitor readministration in non-small-cell lung cancer with acquired resistance

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Abstract

There is no consensus in the salvage treatment for non-small-cell lung cancer (NSCLC) with acquired resistance to primary epidermal growth factor receptor–tyrosine kinase inhibitors (EGFR-TKIs). Fifty-one consecutive EGFR-mutated NSCLC patients with TKI retreatment after acquired resistance were enrolled in this study. The quantitation of mutation abundance was performed by real-time fluorescent quantitative PCR. The correlation between mutation abundance and outcomes of readministrated TKI was analyzed by survival analysis. Patients with high (H) mutation abundance (24/51) had a significantly (log-rank, P < 0.05) longer (5.27–2.53 months) median progression-free survival (PFS), compared with the low (L) abundance group (27/51), whereas the median overall survival showed no difference (21.00–18.20 months, log-rank P = .403) between the two groups. Objective response and disease control rates in group H and group L regarding the second round TKI treatment were 8.3, 70.8 and 0, 48.1 %, respectively. Groupings with different mutation abundances were significantly associated with PFS under multivariate Cox proportional hazards regression model [hazard ratio (HR) for group H vs. L, 0.527; P = .036]. Mutation abundance affects the efficacy of EGFR-TKIs readministration in NSCLC with acquired resistance. The quantitative mutation abundance of EGFR may be a potential predictor for selecting optimal patients to readministrate EGFR-TKIs after acquired resistance to primary TKI.

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Acknowledgments

This work was supported by National High Technology Research and Development Program of China (863 Program) (2012AA02A502).

Conflict of interest

The authors declare that there is no conflict of interest.

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Authors and Affiliations

  1. State Key Laboratory of Oncology in Southern China, Department of Thoracic Surgery, Sun Yat-Sen University Cancer Center, Guangzhou, China

    Ze-Rui Zhao, Yong-Bin Lin, Xiao-Dong Su, Long Jiang, Yi-Gong Zhang & Hao Long

  2. Lung Cancer Research Center, Sun Yat-Sen University, Guangzhou, China

    Ze-Rui Zhao, Yong-Bin Lin, Fang Wang, Sha Fu, Xiao-Dong Su, Long Jiang, Yi-Gong Zhang, Jian-Yong Shao & Hao Long

  3. Department of Cardiothoracic Surgery, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China

    Jin-Feng Wang

  4. State Key Laboratory of Oncology in Southern China, and Department of Molecular Diagnostics, Sun Yat-Sen University Cancer Center, Guangzhou, China

    Fang Wang, Sha Fu & Jian-Yong Shao

  5. Department of Surgical Oncology, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China

    Shu-Lin Zhang

Authors
  1. Ze-Rui Zhao
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  2. Jin-Feng Wang
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  4. Fang Wang
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  7. Xiao-Dong Su
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  8. Long Jiang
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  9. Yi-Gong Zhang
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  10. Jian-Yong Shao
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  11. Hao Long
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Corresponding author

Correspondence to Hao Long.

Additional information

Ze-Rui Zhao, Jin-Feng Wang and Yong-Bin Lin have contributed equally to this work.

Electronic supplementary material

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12032_2013_810_MOESM1_ESM.tif

Supplementary Fig. 1. Patterns of response among individual patients Group H, high EGFR abundance group; Group L, low EGFR abundance group; TKI, tyrosine kinase inhibitor; chemo, chemotherapy; PFS, progression-free survival (TIFF 4887 kb)

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Zhao, ZR., Wang, JF., Lin, YB. et al. Mutation abundance affects the efficacy of EGFR tyrosine kinase inhibitor readministration in non-small-cell lung cancer with acquired resistance. Med Oncol 31, 810 (2014). https://doi.org/10.1007/s12032-013-0810-6

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  • DOI: https://doi.org/10.1007/s12032-013-0810-6

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