FLOT

Background

FLOT4-AIO. Phase III RCT enrolled 716 patients with clinical stage cT2 or higher and/or node-positive (cN+), resectable gastric or GE junction adenocarcinoma, comparing perioperative FLOT with the prior standard ECF/ECX.

Interventions and follow up

Arm A: 4 pre-op and 4 post-op cycles of FLOT (5-FU 2600 mg/m² 24-h infusion D1 + leucovorin 200 mg/m² + oxaliplatin 85 mg/m² + docetaxel 50 mg/m²), Q14
Arm B: 3 pre-op and 3 post-op cycles of ECF/ECX (epirubicin 50 mg/m² + cisplatin 60 mg/m² D1 + fluorouracil 200 mg/m² continuous infusion D1-21, or capecitabine 1250 mg/m² orally D1-21), Q21
Primary endpoint: Overall survival
mFollow up: 43 mo

Results

mOS: 50 mo vs 35 mo (arm A vs B); HR 0.77; 95%CI 0.63–0.94; P=.012
2-yr OS: 68% vs 59%
3-yr OS: 57% vs 48%
5-yr OS: 45% vs 36%

Adverse events

Higher with ECF/ECX (arm B): Grade≥3 nausea 16% vs 7%, vomiting 8% vs 2%, thromboembolic events 6% vs 3%, anemia 6% vs 3%
Higher with FLOT (arm A): Grade≥3 neutropenia 51% vs 39%, infections 18% vs 9%, diarrhea 10% vs 4%, neuropathy 7% vs 2%
Surgical/treatment delivery: Postoperative complications 51% vs 50%; completed adjuvant chemotherapy 46% vs 37%

Conclusions

Perioperative FLOT significantly improved overall survival versus ECF/ECX in resectable gastric and GE junction adenocarcinoma, establishing FLOT as the standard of care.

Key Limitations

ECF/ECX comparator is now considered suboptimal; higher rates of neutropenia, infection, and neuropathy with FLOT; younger, fitter trial population may limit generalizability to older or frailer patients; no biomarker selection.

Clinical Context

FLOT4 established perioperative FLOT as the global standard for resectable gastric/GE junction adenocarcinoma, endorsed in ESMO and ASCO guidance. The ESOPEC trial later showed perioperative FLOT superior to neoadjuvant CROSS chemoradiation for resectable esophageal/GE junction adenocarcinoma.

References