Oncotarget

Research Papers:

Association between miR-31-3p expression and cetuximab efficacy in patients with KRAS wild-type metastatic colorectal cancer: a post-hoc analysis of the New EPOC trial

Siân Pugh, Raphaële Thiébaut _, John Bridgewater, Marie-Lise Grisoni, Karwan Moutasim, Francis Rousseau, Gareth J. Thomas, Gareth Griffiths, François Liebaert, John Primrose and Pierre Laurent-Puig

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Oncotarget. 2017; 8:93856-93866. https://doi.org/10.18632/oncotarget.21291

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Abstract

Siân Pugh1,*, Raphaële Thiébaut2,*, John Bridgewater3,*, Marie-Lise Grisoni2, Karwan Moutasim4, Francis Rousseau2, Gareth J. Thomas4, Gareth Griffiths5, François Liebaert2, John Primrose1,* and Pierre Laurent-Puig6,7,*

1University Surgery, Cancer Sciences, University of Southampton, Southampton, United Kingdom

2IntegraGen SA, Evry, France

3UCL Cancer Institute, London, United Kingdom

4Cancer Sciences Division, University of Southampton, Southampton, United Kingdom

5Southampton Clinical Trials Unit, University of Southampton, Southampton, United Kingdom

6UMR-S1147, University Paris Descartes, Paris, France

7Assistance Publique-Hôpitaux de Paris, Hôpital Georges Pompidou, Paris, France

*These authors have contributed equally to this work

Correspondence to:

Raphaële Thiébaut, email: raphaele.thiebaut@integragen.com

Keywords: metastatic colorectal cancer, biomarker, miR-31-3p, anti-EGFR, cetuximab

Received: March 22, 2017    Accepted: August 27, 2017    Published: September 27, 2017

ABSTRACT

Background: High miR-31-3p expression is associated with inferior outcomes in KRAS wild-type (WT) advanced colorectal cancer patients treated with anti-EGFR therapy. This study evaluated miR-31-3p expression in patients with operable colorectal liver metastases (LM) enrolled in the New EPOC study.

Methods: MiR-31-3p expression was measured in primary tumors (PT) from 149 KRAS WT patients including 71 receiving chemotherapy alone (CT) and 78 receiving chemotherapy plus cetuximab (CTX). Each treatment arm was split into tertiles based on miR-31-3p expression levels. MiR-31-3p expression was also measured in LM from 94 patients with tumor tissue available.

Results: The median progression-free survival for the combined populations with mid or high miR-31-3p expression was shorter in the CTX versus the CT arm (26.7 months versus 12.3 months, HR=2.28 95%CI 1.27; 4.09 p=0.006). Low miR-31-3p expressers had similar outcomes irrespective of treatment (HR=1.06 95%CI 0.43; 2.61 p=0.9). MiR-31-3p expression was correlated between paired PT and LM samples in the CT group but not in the CTX group.

Conclusions: Patients with low miR-31-3p expression in the New EPOC study were not harmed by the addition of cetuximab. This supports miR-31-3p as a promising predictive biomarker for anti-EGFR therapy in KRAS WT advanced colorectal cancer.


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