In a German phase III trial (ESOPEC) reported in The New England Journal of Medicine, Hoeppner et al found that perioperative chemotherapy with fluorouracil/leucovorin/oxaliplatin/docetaxel (FLOT) improved overall survival vs preoperative chemoradiotherapy in patients undergoing surgery for locally advanced esophageal carcinoma.
Study Details
In the open-label multicenter trial, 438 patients were randomly assigned between February 2016 and April 2020 to receive FLOT (n = 221) or preoperative chemoradiotherapy. FLOT consisted of four 2-week cycles of chemotherapy before surgery and four 2-week cycles of chemotherapy after surgery; each cycle consisted of fluorouracil at 2,600 mg/m2, leucovorin at 200 mg/m2, oxaliplatin at 85 mg/m2, and docetaxel at 50 mg/m2 on day 1. Preoperative chemoradiotherapy consisted of carboplatin area under the curve = 2 and paclitaxel at 50 mg/m2 once weekly on days 1, 8, 15, 22, and 29 plus concurrent external-beam radiotherapy at 41.4 Gy (23 fractions of 1.8 Gy per day). The primary endpoint was overall survival.
Key Findings
Median follow-up was 55 months. Overall survival at 3 years was 57.4% (95% confidence interval [CI] = 50.1%–64.0%) in the FLOT group vs 50.7% (95% CI = 43.5%–57.5%) in the preoperative chemoradiotherapy group (hazard ratio [HR] = 0.70, 95% CI = 0.53–0.92, P = .01). Rates at 5 years were 50.6% vs 38.7%. Median overall survival was 66 months (95% CI = 36 months to not estimable) vs 37 months (95% CI = 28–43 months).
Progression-free survival at 3 years was 51.6% (95% CI = 44.3%–58.4%) in the FLOT group vs 35.0% (95% CI = 28.4%–41.7%) in the preoperative chemoradiotherapy group (HR = 0.66, 95% CI = 0.51–0.85).
Grade ≥ 3 adverse events were observed in 58.0% of the FLOT group vs 50.0% of the preoperative chemoradiotherapy group. The most common were neutropenia (19.8%), diarrhea (6.8%), leukopenia (6.3%), and pneumonia (5.8%) in the FLOT group and leukopenia (9.7%), pneumonia (9.2%), and pleural effusion (3.1%) in the preoperative chemoradiotherapy group. Serious adverse events occurred in 47.3% vs 41.8% of patients. Mortality at 90 days after surgery was 3.1% vs 5.6%.
The investigators concluded: “Perioperative chemotherapy with FLOT led to improved survival among patients with resectable esophageal adenocarcinoma as compared with preoperative chemoradiotherapy.”
Jens Hoeppner, MD, Department of Surgery, University Medical Center Ostwestfalen-Lippe–Campus Hospital Lippe, University of Bielefeld, Detmold, is the corresponding author for The New England Journal of Medicine article.
Disclosure: The study was funded by the German Research Foundation. For full disclosures of all study authors, visit www.nejm.org.
