4004 Background: The MAGIC trial established perioperative (periop) epirubicin, cisplatin, and 5-FU (ECF) as a standard treatment for patients (pts) with operable esophagogastric cancer, but survival continues to remain poor. FLOT4 (NCT01216644) is a multicenter, randomized, 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 resectable gastric or GEJ adenocarcinoma. Methods: Eligible pts of stage ≥cT2 and/or cN+ were randomized to either 3 preoperative and 3 post-operative 3-week cycles of ECF/ECX (epirubicin 50 mg/m2, cisplatin 60 mg/m², both d1, and 5-FU 200 mg/m² as continuous infusion or capecitabine 1250 mg/m2 orally d1-21) or 4 pre-operative and 4 post-operative 2-week cycles of FLOT (docetaxel 50 mg/m2, oxaliplatin 85 mg/m², leucovorin 200 mg/m², and 5-FU 2600 mg/m² as 24-hour infusion, all d1). The primary endpoint was overall survival (OS; 80% power; HR of 0.76; 2-sided log-rank test at 5% type I error). Results: Between Aug 2010 and Feb 2015, 716 pts (360 ECF/ECX; 356 FLOT) were randomly allocated. Baseline characteristics were similar between arms (overall, male 74%; median age 62; cT3/T4 81%; cN+ 80%; GEJ 56%). 91% and 37% of pts with ECF/ECX and 90% and 50% with FLOT completed planned pre-operative and post-operative cycles, respectively. Median follow-up was 43 mon. 369 pts died (203 ECF/ECX; 166 FLOT). FLOT improved OS (mOS, 35 mon with ECX/ECF vs. 50 mon with FLOT; HR 0.77 [0.63 - 0.94]; p = 0.012). 3y OS rate was 48% with ECF/ECX and 57% with FLOT. FLOT also improved PFS (mPFS, 18 mon with ECX/ECF vs. 30 mon with FLOT; HR 0.75 [0.62 - 0.91]; p = 0.004). Periop complications were 50% with ECF/ECX and 51% with FLOT. 30- and 90-day mortality was 3% and 8% with ECF/ECX and 2% and 5% with FLOT. There was more G3/4 nausea and vomiting with ECF/ECX and more G3/4 neutropenia with FLOT. Conclusion: Periop FLOT improved outcome in patients with resectable gastric and GEJ cancer compared to periop ECF/ECX. Clinical trial information: NCT01216644.

Biweekly fluorouracil, folinic acid, and oxaliplatin is active and well-tolerated in patients with advanced gastric cancer. Response rates, time to progression, and overall survival were comparable to those achieved with other combination chemotherapy regimens, including FOLFOX6, with significantly less toxicity.