543P - miR-31-3p is a predictive biomarker of cetuximab effects in a post-hoc analysis in the new EPOC study

Date 29 September 2014
Event ESMO 2014
Session Poster Display session
Topics Anti-Cancer Agents & Biologic Therapy
Colon Cancer
Rectal Cancer
Translational Research
Presenter Pierre Laurent-Puig
Citation Annals of Oncology (2014) 25 (suppl_4): iv167-iv209. 10.1093/annonc/mdu333
Authors P. Laurent-Puig1, J.A. Bridgewater2, J. Primrose3, S. Pugh4, G.J. Thomas5, K. Moutasim5, F. Rousseau6, K. Fontaine6, C. Vazart6, V. Decaulne6, A. Leclair6, B. Genin6, S. Imbeaud7, F. Liebaert8, B. Piasecka6, R. Thiébaut6
  • 1Umr-s 1147 Personnalized Medecine, Pharmacogenomics And Therapeutic Optimization), Paris Descartes University, 75270 - Paris Cedex/FR
  • 2Medical Oncology, UCL Cancer Institute, University College London, UK WC1E 6DD - LONDON/GB
  • 3Surgical Unit, Southampton General Hospital Southampton University Hospitals NHS Trust, southampton/GB
  • 4Surgical Unit, University of Southampton, southampton/GB
  • 5Cancer Science Unit, University of Southampton, southampton/GB
  • 6R&d, Integragen, Evry/FR
  • 7Umr-s674, INSERM, Paris/FR
  • 8Integragen Sa, IntegraGen SA, Evry/FR

Abstract

Aim

miR-31-3p expression has been associated with progression-free survival (PFS) in KRAS wild type (WT) mCRC patients treated with anti-EGFR therapies. We evaluated the predictive value of miR-31-3p on PFS in the New EPOC trial by measuring its expression in primary tumors and liver metastases.

Methods

miR-31-3p expression was measured and KRAS/NRAS status was determined in 158 patients. 76 patients received oxaliplatin or irinotecan-based chemotherapy and 82 received the above plus cetuximab. Correlations between low/high miRNA expression and PFS were estimated using a Cox model. Liver metastases were available for 73 of the 158 patients. Regression model was used to compare expression in primary and metastatic tumors.

Results

In patients with high miR-31-3p expression, PFS was significantly shorter in the chemotherapy plus cetuximab treated arm versus the chemotherapy arm (p = 0.02; HR = 2.7, CI95% [1.1–6.4], median PFS: 13.5 and >35 months respectively). In patients with low miR-31-3p expression, PFS was not different between the two arms. There was a significant interaction between treatment arm and miR31-3p expression (HR = 1.7, p = 0.08). There was no significant difference in miR-31-3p expression between the two arms neither in primary tumors (p = 0.7) nor in metastases (p = 0.8). miR-31-3p expression was significantly lower in metastases than in primaries both for chemotherapy plus cetuximab and chemotherapy arms (p = 1.1e-5 and p = 4.2e-7 respectively). Study of miR-31-3p expression in primary tumors and matching metastasis showed correlation in the chemotherapy arm (r = 0.6, p = 10e-5) but not in the chemotherapy plus cetuximab arm (r = 0.1, p = 0.47).

Conclusions

We demonstrated that miR-31-3p expression is predictive of cetuximab effects. Furthermore, we identified a subgroup of patients with high miR-31-3p expression in which cetuximab with chemotherapy had a detrimental effect on PFS. The correlation of miR-31-3p expression in metastases and primary tumors in the chemotherapy arm, but not in the chemotherapy plus cetuximab arm, suggests that cetuximab affects on miR-31-3p expression, supporting its involvement in the EGFR pathway.

Disclosure

P. Laurent-Puig: consultant or advisory for Merck Serono, Amgen, Sanofi, IntegraGen; J.A. Bridgewater: consultant or advisory Relationship in Roche, Merck, Sanofi, Astra Zeneca; J. Primrose: consultant or advisory Relationship for Sanofi Aventis, Bayer, Roche, Merck; F. Rousseau, K. Fontaine, C. Vazart, V. Decaulne, A. Leclair, B. Genin, S. Imbeaud, F. Liebaert, B. Piasecka, R. Thiébaut: Integragen employee. All other authors have declared no conflicts of interest.