Prognostic and predictive value of the Immunoscore in stage III colon cancer patients treated with oxaliplatin in the prospective IDEA France PRODIGE-GERCOR cohort study

Franck Pagès (1, 2) , Thierry André (3, 4) , Julien Taieb (2, 1) , Déwi Vernerey (5) , Julie Henriques (5) , Christophe Borg (6) , Florence Marliot (2) , R. Ben Jannet (7, 8) , Christophe Louvet (9) , Laurent Mineur (10) , Jaafar Bennouna (11) , Jérôme Desrame (12) , Roger Faroux (13) , Amos Kirilovsky (2) , Alex Duval (14, 15) , Pierre F. Laurent-Puig (2, 1) , Magali Svrcek (14, 15, 3) , Fabienne Hermitte , A. Catteau , Jérôme Galon (2) , Jean François J.F. Emile (7)

1 HEGP - Hôpital Européen Georges Pompidou [APHP]
2 CRC (UMR_S_1138 / U1138) - Centre de Recherche des Cordeliers
3 CHU Saint-Antoine [AP-HP]
4 SU FM - Sorbonne Université - Faculté de Médecine
5 CHRU Besançon - Centre Hospitalier Régional Universitaire de Besançon
6 RIGHT - Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098)
7 BECCOH - Biomarqueurs et essais cliniques en Cancérologie et Onco-Hématologie
8 Hôpital Ambroise Paré [AP-HP]
9 IMM - Institut Mutualiste de Montsouris
10 Institut Sainte Catherine [Avignon]
11 CHU Nantes - Centre Hospitalier Universitaire de Nantes
12 Hôpital privé Jean Mermoz
13 Service de gastroentérologie (CHD Vendee - Hopital Les Oudairies, La Roche Sur Yon)
14 CRSA - Centre de Recherche Saint-Antoine
15 Instabilité des microsatellites et cancers [CRSA]

Background: The Immunoscore (IS), which prognostically classifies stage I–III colon cancer (CC) patients, was evaluated in the International Duration Evaluation of Adjuvant Therapy (IDEA) France cohort study investigating 3 versus 6 months of oxaliplatin-based adjuvant chemotherapy in stage III CC patients. Patients and methods: Densities of CD3+ and CD8+ T cells in the tumor and invasive margin were determined by immunohistochemistry, quantified by digital pathology, and converted to IS. Mismatch repair status was determined by immunohistochemistry or by pentaplex PCR. Prediction of disease-free survival (DFS) by IS was analyzed by a multivariable Cox regression model in each study arm. Harrell's C-statistics were used to investigate the IS performance. Results: Samples of 1322 patients were available. IS Low, Intermediate (Int), and High were observed in 43.6%, 47.0%, and 9.4% of patients, respectively. IS Low identified patients at higher risk of relapse or death compared with Int + High [hazard ratio (HR) = 1.54; 95% confidence interval (CI) 1.24–1.93, P = 0.0001]. The 3-year DFS was 66.80% (95% CI 62.23–70.94) for IS Low and 77.14% (95% CI 73.50–80.35) for IS Int + High. In multivariable analysis, IS remained significantly independently associated with DFS (P = 0.003) when adjusted for sex, histological grade, T/N stage, and microsatellite instability. For mFOLFOX6-treated patients (91.6% of the cohort), a statistical significant interaction was observed for the predictive value of IS for treatment duration (3 versus 6 months) in terms of DFS (P = 0.057). IS Int + High significantly predicted benefit of 6 months of treatment (HR = 0.53; 95% CI 0.37–0.75; P = 0.0004), including clinically low- and high-risk stage III CC (all P < 0.001). Conversely, patients with IS Low (46.4%) did not significantly benefit from the 6-month mFOLFOX6 versus the 3-month mFOLFOX6. Conclusions: The prognostic value of IS for DFS was confirmed in patients with stage III CC treated with oxaliplatin-based chemotherapy. Its predictive value for DFS benefit of longer duration of mFOLFOX6 adjuvant treatment was found in IS Int + High. These results will be validated in an external independent cohort. ClinicalTrials.gov registration: NCT03422601; EudraCT Number: 2009-010384-16.

Mots clés: colon cancer; biomarker; chemotherapy; Immunoscore; predictive; prognostic

Domaines: Cancer; Hépatologie et Gastroentérologie

Franck Pagès, Thierry André, Julien Taieb, Déwi Vernerey, Julie Henriques, et al.. Prognostic and predictive value of the Immunoscore in stage III colon cancer patients treated with oxaliplatin in the prospective IDEA France PRODIGE-GERCOR cohort study. Annals of Oncology, 2020, 31 (7), pp.921-929. ⟨10.1016/j.annonc.2020.03.310⟩. ⟨hal-02927418⟩