Perioperative Chemotherapy vs. Preoperative Chemoradiotherapy for Resectable Esophageal Carcinoma

Including radiation therapy in the preoperative treatment of gastroesophageal adenocarcinoma resulted in no survival benefit over chemotherapy alone in the previously reported NEO-AEGIS (NEJM JW Oncol Hematol Oct 20 2023 and Lancet Gastroenterol Hepatol 2023; 8:1015) and TOPGEAR (NEJM JW Oncol Hematol Oct 16 2024 and N Engl J Med 2024; 391:1810) trials. Investigators now report results of the multicenter, phase 3 ESOPEC trial in which patients with esophageal or gastroesophageal junction (GEJ) adenocarcinoma were randomized to perioperative treatment with FLOT chemotherapy (fluorouracil, leucovorin, oxaliplatin, and docetaxel) or preoperative chemoradiotherapy with carboplatin, paclitaxel, and radiotherapy (41.4 Gy).

Of the 438 patients, 80% had clinical stage T3–4 disease, 80% were node positive, 46% had esophageal or Siewert I GEJ primaries, and 31% had Siewert II GEJ primaries. On the FLOT arm, 89% of patients completed all preoperative chemotherapy and 53% completed all postoperative chemotherapy; on the chemoradiotherapy arm, 89% completed all planned radiotherapy and 68% completed all planned chemotherapy.

The primary endpoint of overall survival was superior with FLOT compared with chemoradiotherapy at 3 years (57.4% vs. 50.7%; hazard ratio, 0.70; P=0.01) and at 5 years (50.6% vs. 38.7%). The survival benefit with FLOT was seen across planned subgroups. Progression-free survival at 3 years was also superior with FLOT compared with chemoradiotherapy (51.6% vs. 35.0%; HR, 0.66), as was pathologic complete response (16.7% vs. 10.1%, respectively). No new safety signals were observed.