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Epidemiology and innovations in biomarker development (ID 42)
- Event: ELCC 2017
- Type: Poster Discussion session
- Presentations: 1
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): E. Bria
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.
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.
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
rnrn rn PFSrn PFSrn OSrn OSrn rnrn Univariatern Multivariatern Univariatern Multivariatern rnrnrn HR (95%CI) p-valuern HR (95%CI) p-valuern HR (95%CI) p-valuern HR (95%CI) p-valuern rnrn KRASwt/LKB1wtrn referencern rn rn rn rnrn KRASmut/LKB1wtrn 0.76 (0.51-1.15) p 0.19rn 0.79 (0.51-1.22) p 0.29rn 0.78 (0.51-1.19) p 0.25rn 0.75 (0.49-1.17) p 0.21rn rnrn KRASwt/LKB1mutrn 1.42 (0.68-2.95) p 0.35rn 1.43 (0.67-3.08) p 0.35rn 1.69 (0.81-3.52) p 0.16rn 1.59 (0.75-3.4) p 0.23rn rnrn KRASmut/LKB1mutrn 1.18 (0.64-2.19) p 0.59rn 1.29 (0.67-2.49) p 0.45rn 1.32 (0.72-2.45) p 0.37rn 1.34 (0.69-2.61) p 0.38rn rnrn KRASwt/tp53wtrn referencern rn rn rn rnrn KRASmut/tp53wtrn 0.80 (0.49-1.31) p 0.37rn 0.87 (0.51-1.46) p 0.86rn 0.88 (0.53-1.46) p 0.61rn 0.85 (0.50-1.46) p 0.56rn rnrn KRASwt/tp53mutrn 1.23 (0.79-1.91) p 0.35rn 1.41 (0.88-2.26) p 0.15rn 1.38 (0.88-2.16) p 0.15rn 1.55 (0.95-2.55) p 0.81rn rnrnrn KRASmut/tp53mutrn 1.07 (0.62-1.82) p 0.81rn 1.11 (0.64-1.94) p 0.70rn 1.14 (0.66-1.98) p 0.64rn 1.12 (0.63-1.97) p 0.70rn
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
AIRC (Associazione Italiana Ricerca Cancro)
All authors have declared no conflicts of interest.