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A. Busico



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    Epidemiology and innovations in biomarker development (ID 42)

    • Event: ELCC 2017
    • Type: Poster Discussion session
    • Track:
    • Presentations: 1
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      LBA3 - Correlation between clinical outcomes of patients treated within the tailor trial and next-generation sequencing (NGS) results: Analysis of genes associated to KRAS mutations (ID 463)

      16:45 - 17:45  |  Author(s): A. Busico

      • Abstract

      Background:
      TAILOR (NCT00637910) was a phase 3 randomized trial comparing erlotinib over docetaxel in second line treatment in EGFR wild-type patients. The prognostic and predictive value of KRAS is still debatable. Taking advantage from the available tissue samples and clinical data of this trial, we performed sequencing of a customized gene panel in order to identify novel biomarkers and new potential therapeutic targets specifically associated to KRAS.

      Methods:
      NGS was performed on PGM Ion Torrent platform and involved 111 genes. 5% of frequency was used to define mutations. Association with clinical features or between genes was performed with non-parametric test. Cox regression model was used to define the prognostic role of mutated genes on survival.

      Results:
      188 out of 222 randomized patients had available tissue. 134 tissues were successfully sequenced. 3 were EGFR mutated, 47 were KRAS mutated (36%). 68 were in erlotinib arm and 63 in docetaxel arm. Biomarkers associated to KRAS were 21 LKB1 (16%) and 61 p53 (46%). Survival results are described in the table.rnTable: LBA3rn

      rnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrn
      rnPFSPFSOSOS
      UnivariateMultivariateUnivariateMultivariate
      HR (95%CI) p-valueHR (95%CI) p-valueHR (95%CI) p-valueHR (95%CI) p-value
      KRASwt/LKB1wtreferencernrnrn
      KRASmut/LKB1wt0.76 (0.51-1.15) p 0.190.79 (0.51-1.22) p 0.290.78 (0.51-1.19) p 0.250.75 (0.49-1.17) p 0.21
      KRASwt/LKB1mut1.42 (0.68-2.95) p 0.351.43 (0.67-3.08) p 0.351.69 (0.81-3.52) p 0.161.59 (0.75-3.4) p 0.23
      KRASmut/LKB1mut1.18 (0.64-2.19) p 0.591.29 (0.67-2.49) p 0.451.32 (0.72-2.45) p 0.371.34 (0.69-2.61) p 0.38
      KRASwt/tp53wtreferencernrnrn
      KRASmut/tp53wt0.80 (0.49-1.31) p 0.370.87 (0.51-1.46) p 0.860.88 (0.53-1.46) p 0.610.85 (0.50-1.46) p 0.56
      KRASwt/tp53mut1.23 (0.79-1.91) p 0.351.41 (0.88-2.26) p 0.151.38 (0.88-2.16) p 0.151.55 (0.95-2.55) p 0.81
      KRASmut/tp53mut1.07 (0.62-1.82) p 0.811.11 (0.64-1.94) p 0.701.14 (0.66-1.98) p 0.641.12 (0.63-1.97) p 0.70
      rn

      Conclusions:
      In TAILOR, KRAS was not prognostic. The association with LKB1 and p53 does not affect prognosis, while LKB1 mutation could be a negative prognostic factor (HR = 1.39). Further research is needed to prospectively assess this pathway.

      Clinical trial identification:


      Legal entity responsible for the study:
      Fondazione IRCCS Istituto Nazionale Tumori, Milan

      Funding:
      AIRC (Associazione Italiana Ricerca Cancro)

      Disclosure:
      All authors have declared no conflicts of interest.