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Rieke Frank

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    Lunch & Poster Display session (ID 58)

    • Event: ELCC 2019
    • Type: Poster Display session
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 4/11/2019, 12:30 - 13:00, Hall 1
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      147P - Impact on KRAS-subtypes and TP53 mutations on the prognostic value of KRAS/KEAP1 comutations in non-small cell lung cancer (NSCLC) (ID 493)

      12:30 - 13:00  |  Author(s): Rieke Frank

      • Abstract
      • Slides


      Recent studies suggest a devastating impact of KEAP1 mutations on survival in systemically treated advanced NSCLC for both KRAS-comutated and KRAS-wildtype patients. KRAS G12C mutations differ in their co-mutational properties from other KRAS mutations, and TP53 mutations affect the outcome in a subset of NSCLC like ALK-positive NSCLC. We set out this analysis to determine the impact of both KRAS G12C and co-occurring TP53 mutations on the prognostic value of KRAS/KEAP1 comutations.

      a9ded1e5ce5d75814730bb4caaf49419 Methods

      We pooled the data from three different analyses between 2013 and 2018 and looked for patients with stage IV NSCLC for whom survival data was available and who received systemic therapy. The patients had to be diagnosed by a comprehensive next-generation sequencing panel, comprising at least KRAS, KEAP1and TP53 mutations. Median overall survival (mOS) was assessed using Kaplan Meier statistics.

      20c51b5f4e9aeb5334c90ff072e6f928 Results

      We identified 35 patients with KRAS/KEAP1 comutation and available survival data. G12C was detected in 22 patients (62.9%). A co-occurring TP53 mutation could be found in 15 patients (42.9%), and 11 patients (31.4%) presented with both aberrations beside a KEAP1 mutation. 15 patients (42.9%) had neither comutation. The mOS for the whole cohort was 9.8 months (95% CI, 6.3-13.3 months). Neither the presence of a G12C mutation (mOS 9.8 months [5.7-13.4], log rank p = 0.724) nor the presence of a co-occurring TP53 mutation (mOS 9.0 months [5.8-12.2], log rank p = 0.407) had a significant influence on the outcome. For G12C/TP53 beside KEAP1 mutations, there was hardly any difference to the comparison cohort (mOS 9.8 months [5.4-14.2], log rank p = 0.998). Patients without G12C and TP53 had an mOS of 10.4 months (3.6-17.2 months, log rank p = 0.467).

      fd69c5cf902969e6fb71d043085ddee6 Conclusions

      The comutation status of TP53 mutations and/or the presence of the KRAS G12C subtype have no impact on the prognostic value of KRAS/KEAP1-mutated stage IV NSCLC. Further investigations are ongoing to reveal the influence of the mode of systemic therapy in larger cohorts to confirm these findings.

      b651e8a99c4375feb982b7c2cad376e9 Legal entity responsible for the study

      The authors.

      213f68309caaa4ccc14d5f99789640ad Funding

      Has not received any funding.

      682889d0a1d3b50267a69346a750433d Disclosure

      All authors have declared no conflicts of interest.


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