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 Anticancer Agents
Colon and Rectal Cancer
Translational Research
Basic Principles in the Management and Treatment (of cancer)
Therapy
Biological Therapy
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.