Following the MAGIC trial, perioperative chemotherapy with epirubicin and cisplatin plus fluorouracil or capecitabine (ECF/X) has been the standard of care for localized gastric cancer. Now, findings from the FLOT4 trial challenge this paradigm by demonstrating the superiority of fluorouracil, leucovorin, oxaliplatin and docetaxel (FLOT) over ECF/X as perioperative chemotherapy in locally advanced, resectable gastric cancer or gastro-oesophageal junction (GEJ) adenocarcinoma.
In the phase III portion of this trial, 716 patients with histologically confirmed, locally advanced (≥cT2 and/or cN+), resectable disease were randomly allocated to have surgical resection and either three pre-operative and three postoperative cycles of ECF/X (n = 360) or four pre-operative and four post-operative FLOT cycles (n = 356).
At a median follow-up duration of 43 months, overall survival (OS; the primary end point) was significantly longer in the FLOT group than in the ECF/X group (HR 0.77, 95% CI 0.63–0.94; P = 0.012; median OS 50 months versus 35 months). This OS benefit was consistent across subgroups stratified by baseline characteristics, including age, anatomical site, histology and clinical stage. Furthermore, compared with ECF/X, FLOT significantly improved the margin-free resection rate (78% versus 85%; P = 0.016) and disease-free survival (HR 0.75, 95% CI 0.62–0.91; P = 0.0036; median DFS 18 months versus 30 months).
Similar rates of serious (grade 3 or 4) treatment-related adverse events (27% in both groups), toxic deaths (<1% in both groups) and hospitalization for toxicities (ECF/X 26% versus FLOT 25%) were reported between arms.
Overall, the findings of FLOT4 suggest that FLOT should replace ECF/X as the standard-of-care pre-operative regimen in patients with locally advanced, resectable gastric cancer or GEJ adenocarcinoma.
Al-Batran, S.-E. et al. Perioperative chemotherapy with fluorouracil plus leucovorin, oxaliplatin, and docetaxel versus fluorouracil or capecitabine plus cisplatin and epirubicin for locally advanced, resectable gastric or gastro-oesophageal junction adenocarcinoma (FLOT4): a randomised, phase 2/3 trial. Lancet https://doi.org/10.1016/S0140-6736(18)32557-1 (2019)
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Bradley, C.A. Perioperative FLOT superior to ECF/X. Nat Rev Clin Oncol 16, 465 (2019). https://doi.org/10.1038/s41571-019-0215-3