Author of

• 19960

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  Epidemiology and innovations in biomarker development (ID 42)

  • Event: ELCC 2017
  • Type: Poster Discussion session
  • Track:
  • Presentations: 1
  • Moderators:P. Boffetta, S. Lantuejoul, R.A. Stahel
  • Coordinates: 5/06/2017, 16:45 - 17:45, Room W

  • 19961

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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 - 16:45  |  Author(s): G. Sozzi
    • 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

    rn	PFS	PFS	OS	OS
    	Univariate	Multivariate	Univariate	Multivariate
    	HR (95%CI) p-value	HR (95%CI) p-value	HR (95%CI) p-value	HR (95%CI) p-value
    KRASwt/LKB1wt	reference	rn	rn	rn
    KRASmut/LKB1wt	0.76 (0.51-1.15) p 0.19	0.79 (0.51-1.22) p 0.29	0.78 (0.51-1.19) p 0.25	0.75 (0.49-1.17) p 0.21
    KRASwt/LKB1mut	1.42 (0.68-2.95) p 0.35	1.43 (0.67-3.08) p 0.35	1.69 (0.81-3.52) p 0.16	1.59 (0.75-3.4) p 0.23
    KRASmut/LKB1mut	1.18 (0.64-2.19) p 0.59	1.29 (0.67-2.49) p 0.45	1.32 (0.72-2.45) p 0.37	1.34 (0.69-2.61) p 0.38
    KRASwt/tp53wt	reference	rn	rn	rn
    KRASmut/tp53wt	0.80 (0.49-1.31) p 0.37	0.87 (0.51-1.46) p 0.86	0.88 (0.53-1.46) p 0.61	0.85 (0.50-1.46) p 0.56
    KRASwt/tp53mut	1.23 (0.79-1.91) p 0.35	1.41 (0.88-2.26) p 0.15	1.38 (0.88-2.16) p 0.15	1.55 (0.95-2.55) p 0.81
    KRASmut/tp53mut	1.07 (0.62-1.82) p 0.81	1.11 (0.64-1.94) p 0.70	1.14 (0.66-1.98) p 0.64	1.12 (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.