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Perioperative Therapy With FLOT vs ECF/ECX in Locally Advanced Gastric Adenocarcinoma

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Key Points

  • FLOT was associated with significantly prolonged overall survival vs ECF/ECX.
  • Median overall survival was 50 vs 35 months.

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.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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