Author of

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  P2.01 - Advanced NSCLC (Not CME Accredited Session) (ID 950)

  • Event: WCLC 2018
  • Type: Poster Viewing in the Exhibit Hall
  • Track:
  • Presentations: 1
  • Moderators:
  • Coordinates: 9/25/2018, 16:45 - 18:00, Exhibit Hall

  • 26842

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    P2.01-44 - Prognostic Value of TP53 Hot Exon Mutation in Patients with Advanced Non-Small Cell Lung Cancer (NSCLC) (ID 13150)

    16:45 - 18:00  |  Author(s): Fang Xu
    • Abstract
    • Slides

    Background
    

    Numerous studies have revealed either very marginal or no prognostic value of TP53 mutation NSCLC patients. Currently, in clinical settings, all TP53 mutations have been considered equally, without any differentiation between the various types and positions of mutations. However, increasing evidence has triggered us to challenge such practice.

    a9ded1e5ce5d75814730bb4caaf49419 Method
    

    We retrospectively investigated the correlation between mutations occurring at hot exons (5-8) and overall survival (OS) in 214 previously tyrosine kinase inhibitor (TKI) treated advanced NSCLC patients. Among them, 184 had 1 line of TKI-treatment and the remaining 30 patients had more than 1 line of TKI-treatment. 115 harbored TP53 mutation; among them 105 patients had concurrent EGFR mutation; 5 had ALK rearrangements; 1 had ROS1 rearrangements; 1 had KRAS and 2 had ERBB2 mutations. 99 patients had wild type (WT) TP53; among them, 92 had EGFR mutation, 4 with ALK-rearrangements, 1 with MET and 1 with BRAF mutation. Fisher’s exact test and the Mann-Whitney test were used to determine if categorical and continuous variables, respectively, differed between TP53 WT and mutant groups.

    4c3880bb027f159e801041b1021e88e8 Result
    

    The prevalence of TP53 mutation in our cohort is 53.7% (115/214); 28 had mutation on exon 5, 18 on exon 6, 22 on exon 7 and 32 on exon 8. 32 patients had loss of function mutation and 51 patients had disruptive mutation. Our data revealed a positive correlation with N and M stage. Patients harboring TP53 mutation are more likely to diagnose with more advanced N (p=0.018) and M stage (p=0.001). Furthermore, patients with TP53 mutation are more likely to have liver (p<0.001) and bone metastasis (p=0.012). In patients treated with only 1 line of TKI-treatment, although TP53 status had no effect on PFS (p=0.241) and OS (p=0.49) when they were considered collectively, we observed patients with mutation in exon 5 had shorter OS (p=0.029) and mutation in exon 8 had shorter PFS (P=0.003) after controlling for age, gender, stage and histology. Furthermore, within the osimertinib subgroup (N=101), patients harboring mutation in exon 8 had significantly shorter PFS (P=0.007). In patients treated with more than 1 line of treatment, neither TP53 mutation considered collectively, nor hot exon mutations had correlation with PFS or OS.

    8eea62084ca7e541d918e823422bd82e Conclusion
    

    Our study revealed unfavorable prognostic value of mutations in exon 5 and no prognostic value of TP53 if all mutations were considered collectively. Our study adds new dimension to the emerging picture that not all TP53 mutants are equal.

    6f8b794f3246b0c1e1780bb4d4d5dc53

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