LBA3 - Correlation between clinical outcomes of patients treated within the tailor trial and next-generation sequencing (NGS) results: Analysis of genes a...

Date 06 May 2017
Event ELCC 2017
Session Epidemiology and innovations in biomarker development
Topics Lung and other Thoracic Tumours
Translational Research
Presenter Monica Ganzinelli
Citation Annals of Oncology (2017) 28 (suppl_2): ii69-ii70. 10.1093/annonc/mdx195
Authors M. Ganzinelli1, M. Broggini2, G. Sozzi3, M. Moro3, M. Marabese2, E. Caiola2, A. Busico3, E. Bria4, E. Rulli2, M.C. Garassino1
  • 1Thoracic Oncology, Fondazione IRCCS - Istituto Nazionale dei Tumori, 20133 - Milano/IT
  • 2IRCCS - Istituto di Ricerche Farmacologiche "Mario Negri", Milano/IT
  • 3Fondazione IRCCS - Istituto Nazionale dei Tumori, Milano/IT
  • 4Azienda Ospedaliera Universitaria Integrata Verona-"Borgo Roma", Verona/IT

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.