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

Emeric Boisteau (1) , Alexandra Lespagnol (1) , Marie de Tayrac (2, 1) , Sébastien Corre (2) , Anthony Perrot (1) , Nathalie Rioux-Leclercq (1, 3) , Séverine Martin-Lannerée (4) , Pascal Artru (5) , Philippe Chalabreysse (6) , Pierre-Guillaume Poureau (7) , Laurent Doucet (8) , Dahna Coupez (9, 10) , Jaafar Bennouna (9, 10) , Céline Bossard (10) , Romain Coriat (11) , Frédéric Beuvon (11) , Lucile Bauguion (12) , François Leclair (12) , Romain Chautard (13) , Thierry Lecomte (13, 14) , Serge Guyetant (13, 15) , Romain Desgrippes (16) , Denis Grasset (17) , Hélène Lhostis (17) , Karine Bouhier-Leporrier (18) , Frédéric Bibeau (18) , Julien Edeline (19, 20) , Marie-Dominique Galibert (2, 1) , Astrid Lièvre (1, 21, 22)

1 Centre Hospitalier Universitaire de Rennes [CHU Rennes] = Rennes University Hospital [Ponchaillou]
2 IGDR - Institut de Génétique et Développement de Rennes
3 Irset - Institut de recherche en santé, environnement et travail
4 IntegraGen
5 Hôpital privé Jean Mermoz [Lyon]
6 Cypath : siège social [Villeurbanne]
7 University Hospital Gasthuisberg [Leuven]
8 CHRU Brest - Centre Hospitalier Régional Universitaire de Brest
9 Institut des Maladies de l'Appareil Digestif
10 CHU Nantes - Centre Hospitalier Universitaire de Nantes
11 Hôpital Cochin [AP-HP]
12 CHDV - Centre Hospitalier Départemental Vendée
13 CHRU Tours - Centre Hospitalier Régional Universitaire de Tours
14 GICC EA 7501 - Groupe innovation et ciblage cellulaire (GICC), EA 7501 [2018-...]
15 UMR ISP - Infectiologie et Santé Publique
16 CH de Saint-Malo [Broussais]
17 CHBA - Centre hospitalier Bretagne Atlantique (Morbihan)
18 CHU Caen
19 Centre Hospitalier Universitaire [Rennes]
20 CRLCC - CRLCC Eugène Marquis
21 COSS - Chemistry, Oncogenesis, Stress and Signaling
22 OSS - Oncogenesis, Stress, Signaling

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.

Mots clés: anti-EGFR mAb; bevacizumab; biomarker; colorectal cancer; metastasis; miR-31-3p

Domaines: Sciences du Vivant [q-bio]; Hépatologie et Gastroentérologie; Cancer

Emeric Boisteau, Alexandra Lespagnol, Marie de Tayrac, Sébastien Corre, Anthony Perrot, et al.. MiR-31-3p do not predict anti-EGFR efficacy in first-line therapy of RAS wild-type metastatic right-sided colon cancer. Clinics and Research in Hepatology and Gastroenterology, 2022, 46 (5), 11 p. ⟨10.1016/j.clinre.2022.101888⟩. ⟨hal-03595901⟩