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MiR-31-3p do not predict anti-EGFR efficacy in first-line therapy of RAS wild-type metastatic right-sided colon cancer - 10/06/22

Doi : 10.1016/j.clinre.2022.101888 
Emeric Boisteau a, 1, Alexandra Lespagnol b, 1, Marie De Tayrac b, c, Sébastien Corre c, Anthony Perrot b, Nathalie Rioux-Leclercq d, e, Séverine Martin-Lannerée f, Pascal Artru g, Philippe Chalabreysse h, Pierre-Guillaume Poureau i, Laurent Doucet j, Dahna Coupez k, Jaafar Bennouna k, Céline Bossard l, m, Romain Coriat n, Frédéric Beuvon o, Lucile Bauguion p, François Leclair q, Romain Chautard r, Thierry Lecomte r, s, Serge Guyetant t, u, Romain Desgrippes v, Denis Grasset w, Hélène Lhostis x, Karine Bouhier-Leporrier y, Frédéric Bibeau z, Julien Edeline d, aa, Marie-Dominique Galibert b, c, , 1 , Astrid Lièvre a, ab, , 1
a Department of Gastroenterology, Rennes University Hospital, University Hospital of Pontchaillou, 2 rue Henri Le Guilloux, Rennes 35033 Cedex 09, France 
b Department of Somatic Genetics of Cancer, Department of Molecular Genetics and Genomic, Rennes University Hospital, 2 rue Henri Le Guilloux, Rennes 35033 Cedex 09, France 
c CNRS, IGDR (Institut de Génétique et Développement de Rennes),Université de Rennes, UMR 6290, Rennes F-35000, France 
d University of Rennes 1, Rennes, France 
e Department of Pathological Anatomy and Cytology, Rennes University Hospital, Rennes, France 
f IntegraGen SA, 5, rue Henri Desbruères, Evry, France 
g Digestive Oncology, Private Hospital Jean Mermoz, Lyon, France 
h Philippe Chalabreysse, cabinet de pathologie CYPATH, 201 route de Genas, Villeurbanne 69100, France 
i Department of Oncology, University Hospital, Brest, France 
j Service d'Anatomie et Cytologie Pathologiques, Hôpital Morvan, CHRU Brest, Brest, France 
k Digestive Oncology, Institut Des Maladies De l'Appareil Digestif, Centre Hospitalier Universitaire De Nantes, Nantes, France 
l Service d'Anatomie et cytologie pathologiques, CHU Nantes, Nantes, France 
m Université de Nantes, INSERM CRCINA, Nantes 44000, France 
n Gastroenterology and Digestive Oncology Unit, Hopital Cochin, APHP Centre, Université de Paris, Paris France 
o Department of Pathology, Hôpital Cochin, Assistance Publique-Hôpitaux de Paris, AP-HP Centre-Université de Paris, Paris, France 
p Department of Gastroenterology, Centre Hospitalier Vendée, La Roche-sur-Yon, France 
q Service d'Anatomie et Cytologie Pathologiques, CHD Vendée, France 
r Department of Hepato-Gastroenterology and Digestive Oncology, CHRU de Tours, Tours, France 
s Université de Tours, EA 7501 GICC, Tours, France 
t Service d'Anatomie Pathologique, Hôpital Trousseau, CHRU de Tours, France 
u Université de Tours, INRAE, ISP, Tours F-37000, France 
v Hépato-Gastro-Entérologie, Cancérologie Digestive, Centre Hospitalier de Saint Malo, France 
w Service de Gastroentérologie, Centre Hospitalier Bretagne Atlantique, 20 boulevard Guillaudot, Vannes 56017, France 
x Department of Anatomy and Cytopathology, Centre Hospitalier Bretagne Atlantique, Vannes, France 
y Service d'Hépato-Gastro-Entérologie, CHU Caen, Caen, France 
z Service d'Anatomie et Cytologie pathologiques, CHU de Caen, Université de Caen, Normandie, France 
aa Department of Medical Oncology, Eugène Marquis Anticancer Center, Rennes, France 
ab INSERM U1242 “Chemistry Oncogenesis Stress Signaling”, Rennes 1 University, Rennes, France 

Corresponding author at: Department of Somatic Genetics of Cancer, Department of Molecular Genetics and Genomic, Rennes University Hospital, 2 rue Henri Le Guilloux, Rennes 35033 Cedex 09, France.Department of Somatic Genetics of Cancer, Department of Molecular Genetics and GenomicRennes University Hospital,2 rue Henri Le GuillouxRennes35033 Cedex 09France⁎⁎Corresponding author at: Department of Gastroenterology, Rennes University Hospital, University Hospital of Pontchaillou, 2 rue Henri Le Guilloux, Rennes 35033 Cedex 09, France.Department of GastroenterologyRennes University Hospital,University Hospital of Pontchaillou2 rue Henri Le GuillouxRennes35033 Cedex 09France

Highlights

miR-31-3p expression is predictive of anti-EGFR efficacy in mCRC.
Primary tumor side is prognostic and predictive of anti-EGFR efficacy in mCRC.
In right-sided RAS-wt mCRC, miR-31-3p expression do not predict anti-EGFR efficacy and bevacizumab is the targeted therapy of choice whatever miR-31-3p expression level.

El texto completo de este artículo está disponible en PDF.

Abstract

Background

Low miR-31-3p expression was identified as predictive of anti-EGFR efficacy in RAS-wt mCRC. Primary tumor side was also proposed as a predictive factor of anti-EGFR benefit. This retrospective multicentric study evaluated the predictive role of miR-31-3p in right-sided RAS-wt mCRC patients treated with first-line CT+anti-EGFR or CT+bevacizumab (Beva).

Methods

Seventy-two right-sided RAS-wt mCRC patients treated in first-line with CT+anti-EGFR (n = 43) or Beva (n = 29) were included. Overall survival (OS), progression-free survival (PFS) and response rate (RR) were analyzed and stratified according to tumor miR-31-3p expression level and targeted therapy (TT).

Results

BRAF V600E mutation was more frequent in high vs low miR-31-3p expressers (60.6% vs 15.4%, P < 0.001). PFS was significantly longer with CT+Beva than with CT+anti-EGFR (13 vs 7 months; P = 0.024). Among low miR-31-3p expressers, PFS, OS and RR were not significantly different between the two groups, while in high miR-31-3p expressers, only PFS was longer in the CT+Beva group (11 vs 6 months; P = 0.03). In patients treated with CT+anti-EGFR, low miR-31-3p expressers had a significantly longer OS (20 vs 13 months; P = 0.02) than high miR-31-3p expressers. ORR was not significantly different between the two groups of treatment, in both low and high miR-31-3p expressers. MiR-31-3p expression status was statistically correlated between primary tumors and corresponding metastases.

Conclusion

In this study, miR-31-3p couldn't identify a subgroup of patients with right-sided RAS-wt mCRC who might benefit from anti-EGFR and suggest that Beva is the TT of choice in first-line treatment of these patients.

El texto completo de este artículo está disponible en PDF.

Keywords : Colorectal cancer, Metastasis, Biomarker, miR-31-3p, anti-EGFR mAb, Bevacizumab


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Vol 46 - N° 5

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