Perioperative Therapy With FLOT vs ECF/ECX in Locally Advanced Gastric Adenocarcinoma
In the German phase II/III FLOT4 trial reported in The Lancet, Al-Batran et al found that perioperative therapy with the docetaxel-based triplet FLOT (fluorouracil [5-FU]/leucovorin, oxaliplatin, and docetaxel) was associated with improved overall survival vs ECF/ECX (epirubicin and cisplatin plus either 5-FU or capecitabine) in patients with resectable locally advanced gastric or gastroesophageal junction adenocarcinoma.
Study Details
The open-label trial included 716 patients with advanced clinical stage cT2 or higher or nodal positive stage (cN+), or both, and no evidence of distant metastases. The patients were recruited from 38 sites, and were randomly assigned between August 2010 and February 2015 to FLOT (n = 356) or ECF/ECX (n = 360). FLOT consisted of four preoperative and four postoperative 2-week cycles of docetaxel 50 mg/m², oxaliplatin 85 mg/m², leucovorin 200 mg/m², and 5-FU 2,600 mg/m² as a 24-hour infusion on day 1. ECF/ECX consisted of three preoperative and three postoperative 3-week cycles of epirubicin 50 mg/m², cisplatin 60 mg/m² on day 1, plus either 5-FU 200 mg/m² as continuous infusion or oral capecitabine 1,250 mg/m² on days 1 to 21.
The primary endpoint was overall survival in the intent-to-treat population.
Overall Survival
Median follow-up was 43 months for surviving patients in both groups. Median overall survival was 50 months in the FLOT group vs 35 months in the ECF/ECX group (hazard ratio [HR] = 0.77, P = .012). Estimated overall survival at 2, 3, and 5 years was 68% vs 59%, 57% vs 48%, and 45% vs 36%. Median disease-free survival was 30 months vs 18 months (HR = 0.75, P = .0036).
Adverse Events
Concerning grade 3 or 4 adverse events, the ECF/ECX group had higher rates of nausea (16% vs 7%), vomiting (8% vs 2%), thromboembolic events (6% vs 3%), and anemia (6% vs 3%), and the FLOT group had higher rates of infections (18% vs 9%), neutropenia (51% vs 39%), diarrhea (10% vs 4%), and neuropathy (7% vs 2%). Treatment-related serious adverse events—including those occurring during hospitalization for surgery—occurred in 27% vs 27% of patients. Hospitalization for toxicity occurred in 25% vs 26%. Two patients in each group died from adverse events.
The investigators concluded, “In locally advanced, resectable gastric or gastroesophageal junction adenocarcinoma, perioperative FLOT improved overall survival compared with perioperative ECF/ECX.”
Salah-Eddin Al-Batran, MD, of UCT–University Cancer Center, Frankfurt, is the corresponding author for The Lancet article.
Disclosure: The study was funded by The German Cancer Aid (Deutsche Krebshilfe), Sanofi-Aventis, Chugai, and Stiftung Leben mit Krebs Foundation. For full disclosures of the study authors, visit thelancet.com.
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