Prognostic utility of immune markers and validation of Immunoscore in stage III colon carcinoma patients treated with adjuvant FOLFOX in a phase III trial (NCCTG N0147; Alliance)

Abstract

Background: The MAGIC trial established perioperative (periop) epirubicin, cisplatin, and 5-FU (ECF) as a standard treatment for patients (pts) with operable esophagogas-tric cancer, but survival continues to remain poor. FLOT4 is a multicenter, random-ized, investigator-initiated, phase 3 trial. It compares the docetaxel-based triplet FLOT with the anthracycline-based triplet ECF/ECX as a periop. treatment for pts with resect-able gastric or GEJ adenocarcinoma. Methods: Eligible pts of stage !cT2 and/or cNþ were randomized to either 3 preopera-tive and 3 post-operative 3-week cycles of ECF/ECX (epirubicin 50 mg/m 2 , cisplatin 60 mg/m 2 , both d1, and 5-FU 200 mg/m 2 as continuous infusion or capecitabine 1250 mg/m 2 orally d1-21) or 4 pre-operative and 4 post-operative 2-week cycles of FLOT (docetaxel 50 mg/m 2 , oxaliplatin 85 mg/m 2 , leucovorin 200 mg/m 2 , and 5-FU 2600 mg/m 2 as 24-hour infusion, all d1). The primary endpoint was overall survival (OS). Funded by Deutsche Krebshilfe. Results: Between Aug 2010 and Feb 2015, 716 pts (360 ECF/ECX; 356 FLOT) were randomly allocated. Baseline characteristics were well balanced. 91% and 44% of pts with ECF/ECX and 90% and 51% with FLOT completed pre-operative and post-operative cycles, respectively. Median follow-up was 43 mon. FLOT increased the rate of complete marginal free (R0) resection (ECF/ECX 77%, FLOT 48%; p ¼ 0.011) and improved OS (mOS, 35 mon with ECX/ECF vs. 50 mon with FLOT; HR 0.77 [0.63-0.94]; p ¼ 0.012), and PFS (mPFS, 18 mon with ECX/ECF vs. 30 mon with FLOT; HR 0.75 [0.62-0.91]; p ¼ 0.004). 3y OS rate was 48% with ECF/ECX and 57% with FLOT. Downsizing also favored FLOT with tumors