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Impact of TP53 Mutations on EGFR-Tyrosine Kinase Inhibitor Efficacy and Potential Treatment Strategy

  • Author Footnotes
    # These authors contributed equally to this work
    Jing Fu
    Footnotes
    # These authors contributed equally to this work
    Affiliations
    Department of Oncology, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, People's Hospital of Henan University, Zhengzhou, Henan Province, China
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  • Author Footnotes
    # These authors contributed equally to this work
    Yuyang Tong
    Footnotes
    # These authors contributed equally to this work
    Affiliations
    Department of Oncology, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, People's Hospital of Henan University, Zhengzhou, Henan Province, China
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  • Author Footnotes
    # These authors contributed equally to this work
    Ziguang Xu
    Footnotes
    # These authors contributed equally to this work
    Affiliations
    Department of Pathology, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, People's Hospital of Henan University, Zhengzhou, Henan Province, China
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  • Author Footnotes
    # These authors contributed equally to this work
    Yaonan Li
    Footnotes
    # These authors contributed equally to this work
    Affiliations
    Department of Emergency, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, People's Hospital of Henan University, Zhengzhou, Henan Province, China
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  • Ya Zhao
    Affiliations
    Department of Oncology, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, People's Hospital of Henan University, Zhengzhou, Henan Province, China
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  • Tao Wang
    Affiliations
    Department of Oncology, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, People's Hospital of Henan University, Zhengzhou, Henan Province, China
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  • Cuidan Li
    Affiliations
    CAS Key Laboratory of Genome Sciences & Information, Beijing Institute of Genomics, Chinese Academy of Sciences, China National Center for Bioinformation, Beijing, China
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  • Shundong Cang
    Correspondence
    Address for correspondence: Shundong Cang, Ph.D., Professor, Department of Oncology, Henan Provincial People's Hospital, No.7, Weiwu Road, Zhengzhou 450003, China.
    Affiliations
    Department of Oncology, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, People's Hospital of Henan University, Zhengzhou, Henan Province, China
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  • Author Footnotes
    # These authors contributed equally to this work
Published:August 14, 2022DOI:https://doi.org/10.1016/j.cllc.2022.08.007

      Abstract

      Background

      We investigated the impact of factors that influence TP53 mutations on the efficacy of EGFR-tyrosine kinase inhibitors and potential treatment strategies.

      Materials and Methods

      Tumor samples were collected to screen gene mutations by next-generation sequencing, as well as the patients’ baseline characteristics. The overall response to treatment with TKIs was evaluated based on interval computed tomography scans at each follow-up time point. A Fisher's exact test and log-rank test were used to determine the statistical differences in this study.

      Results

      A total of 1134 clinical samples were collected from NSCLC patients, and TP53mut was identified in 644 cases and EGFRmut in 622 cases. A low frequency of TP53mut or more than 50% EGFR co-mutation rate were related to the prognosis of TKI-treated patients. In addition, TP53mut in the region outside of the DB domain had the strongest correlation with TKI resistance, whereas various types of mutations in the DB domain only had an impact on PFS. A grouping study of EGFR-TKI-based treatment revealed that EGFR-TKIs with chemotherapy were associated with more significant survival benefits for patients with prognostic TP53mut, whereas EGFR-TKI therapy was favorable for TP53wt patients. Furthermore, TP53mut could shorten the time to the relapse of postoperative patients, who will also likely respond well to EGFR-TKIs with chemotherapy.

      Conclusion

      Various characteristics of TP53mut affect the prognosis of TKI-treated patients to varying degrees. EGFR-TKIs with chemotherapy were benefit for patients’ survival with prognostic TP53mut, which provides an important reference for treatment management of EGFRmut patients.

      Keywords

      Abbreviations:

      TP53mut (TP53 mutation), EGFRmut (EGFR mutation), EGFR-TKIs (EGFR-tyrosine kinase inhibitors), PFS (progression-free survival), OS (overall survival), NSCLC (Non-small cell lung cancer), ORR (the objectiveresponse rate), DCR (disease control rate), NGS (next-generation sequencing), CR (complete response), PR (partial response), SD (stable disease), PD (progressive disease), RFS (Relapse-Free Survival)
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