Multicenter phase 3 trial of perioperative chemotherapy versus preoperative chemoradiotherapy for esophageal cancer

The best multimodal approach for resectable locally advanced esophageal adenocarcinoma is unclear. The phase 3 ESOPEC trial, at 25 centers in Germany, compared perioperative FLOT chemotherapy (fluorouracil, leucovorin, oxaliplatin, and docetaxel) versus preoperative chemoradiotherapy (CRT; 41.4 Gy plus carboplatin and paclitaxel) for patients with cT1 cN+, cT2-4a cN+, or cT2-4a cN0 esophageal adenocarcinoma. The median duration of follow-up was 55 months. The overall survival rate at 3 years was 57.4% in the FLOT group versus 50.7% in the CRT group (HR 0.70; 95% CI 0.53-0.92) whereas the progression-free survival rate at 3 years was 51.5% in the FLOT group versus 35.0% in the CRT group (0.66; 0.51-0.85). Grade 3 or higher treatment-related adverse events were seen in 58.0% of patients in the FLOT group and 50.0% of patients in the CRT group. Mortality at 90 days after surgery was 3.1% in the FLOT group and 5.6% in the CRT group. The authors conclude that among patients with resectable esophageal adenocarcinoma, perioperative FLOT chemotherapy resulted in improved survival as compared with preoperative CRT.