43P - miR31-3p expression in patients with advanced lepidic adenocarcinoma (L-ADC) treated with EGFR TKI in IFCT 0401 and 0504 trials

Date 17 April 2015
Event ELCC 2015
Session Poster lunch
Topics Non-Small-Cell Lung Cancer, Metastatic
Translational Research
Presenter Raphaele Thiebaut
Citation Annals of Oncology (2015) 26 (suppl_1): 10-14. 10.1093/annonc/mdv045
Authors R. Thiebaut1, M. Wislez2, C. Vazart1, V. Decaulne1, J. Mazieres3, S. Friard4, P. Merle5, F. Morin6, F. Liebaert1, J. Cadranel2
  • 1-, IntegraGen, 91000 - Evry/FR
  • 2Pneumologie, APHP, CancerEst, Tenon University Hospital, Paris/FR
  • 3Thoracic Oncology, Hôpital Larrey, Centre Hospitalier Universitaire de Toulouse, Toulouse/FR
  • 4Pneumologie, Hôpital Foch, Suresnes/FR
  • 5Pneumologie, CHU, Clermont-Ferrand/FR
  • 6-, Intergroupe Francophone de Cancérologie Thoracique (IFCT), Paris/FR

Abstract

Aim/Background

miR31-3p expression has been associated with progression-free survival (PFS) in patients with RAS wild-type (WT) metastatic colorectal cancer (mCRC) treated with anti-EGFR. It has been shown that this microRNA might be involved in EGFR pathway. In this study, we evaluate miR31-3p expression in patients with advanced L-ADC treated with EGFR TKI.

Methods

miR31-3p expression was measured by RTQPCR in FFPE primary tumor samples from 48 patients with advanced L-ADC from two randomized phase II trials. All patients were first-line treated by gefitinib in IFCT-0401 (n = 22) or by erlotinib or paclitaxel plus carboplatin in IFCT-0504 (n = 26) with treatment cross-over after progression or toxicity. Effect of miR31-3p expression level on overall survival (OS), progression free survival (PFS) and disease control rate (DCR) was tested using a Cox proportional hazards model. To enlarge the population, a merged data-set was built by pooling patients treated in first-line by EGFR TKI (gefitinib, n = 22; erlotinib, n = 10). Histologic subtype was taken into account to compare effects of miR31-3p in the mucinous (MUC) versus non-mucinous (NMUC) subtypes. A p value <0.1 was considered as significant.

Results

Distribution of miR31-3p expression was comparable in both trials. Considering histological subtype, patients with NMUC tumors showed a significantly lower miR31-3p expression than patients with MUC tumors (p = 0.004). In merged data set, we observed a strong correlation between level of mucine expression in tumor cells assessed by PAS coloration and miR31-3p expression (spearman correlation:0.73; p = 0.0002). Expression of miR31-3p was significantly predictive of DCR (OR = 1.49, p = 0.03). In patients with NMUC tumors, a significant effect of miR31-3p expression was observed in OS (HR = 1.49; p = 0.08).

Conclusions

We showed that in NMUC tumors, expression of miR31-3p was lower than in MUC tumors and that miR31-3p expression has a significant effect on OS in patients treated with EGFR TKI. We showed an effect of miR31-3p expression on DCR in the merged dataset. These results are consistent with those observed in mCRC, and hint that miR31-3p could be marker of interest in L-ADC patients treated with TKI.

Disclosure

R. Thiebaut: Employee of IntegraGen SA; Title: Geneticist, Project Manager.

C. Vazart and V. Decaulne: Employee of IntegraGen SA; Title: Lab Technician.

F. Liebaert: Employee of IntegraGen SA; Title: VP of R&D and Medical Affairs Stock Ownership: IntegraGen SA.

All other authors have declared no conflicts of interest.