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Comparing Perioperative Chemotherapy and Preoperative Chemoradiotherapy in Esophageal Cancer
The optimal preoperative therapy for adenocarcinoma of the esophagus or gastroesophageal junction (GEJ) remains controversial. Standard options include preoperative or perioperative chemotherapy, or combined chemotherapy and radiation therapy followed by surgery.
In the phase 3, multicenter, European NEO-AEGIS trial, patients with operable adenocarcinoma of the esophagus or GEJ and endoscopic ultrasound stage T2–3, N0–3, M0 disease were randomized to perioperative chemotherapy (3 preoperative and 3 postoperative cycles of epirubicin, cisplatin or oxaliplatin, and capecitabine or continuous 5-FU infusion) or preoperative combined chemoradiotherapy (weekly carboplatin and paclitaxel and 41.4 Gy of radiotherapy in 23 fractions). Patients were required to have surgery by en-bloc resection.
Of 362 patients, most had stage T3 (84%) and N1–2 (57%) disease, and most had tumors of the lower esophagus or Siewert type 1 GEJ (69%). In the last years of the study, use of the FLOT regimen (5-FU, leucovorin, oxaliplatin, and docetaxel) was permitted; 15% of patients in the chemotherapy arm received FLOT. The trial was closed prematurely after a second futility analysis for overall survival showed no difference between treatment arms.
At a median follow-up of 38.8 months, median overall survival was similar in the perioperative chemotherapy and chemoradiotherapy arms (48.0 and 49.2 months; hazard ratio, 1.03, P=0.82). Three-year overall survival was also similar (55% and 57%). Although the chemoradiotherapy arm, compared with the chemotherapy arm, had higher rates of pathologic complete response (12% vs. 4%), negative margin resection (96% vs. 82%), and achievement of N0 status (60% vs. 44%), this did not translate into improved survival. The chemotherapy and chemoradiotherapy arms had similar rates of local recurrence (10% and 9%), distant recurrence (21% and 23%), or both (8% and 13%), as well as postoperative complications and mortality.
Comment
NEO-AEGIS is a pivotal trial indicating equipoise for use of either perioperative chemotherapy or chemoradiotherapy in esophageal and GEJ adenocarcinoma, which questions the need for adding radiotherapy to chemotherapy. Better pathologic outcomes with chemoradiotherapy did not translate into improvements in survival or patterns of disease recurrence. It is striking that 4 months of an intensive combination chemotherapy regimen did not improve distant disease recurrence compared with only 5 weekly doses of carboplatin/paclitaxel. We await results of the ESOPEC trial comparing the potentially more effective FLOT regimen to chemoradiotherapy in esophageal adenocarcinoma.
Citation(s)
Author:
Reynolds JV et al.
Title:
Trimodality therapy versus perioperative chemotherapy in the management of locally advanced adenocarcinoma of the oesophagus and oesophagogastric junction (Neo-AEGIS): An open-label, randomised, phase 3 trial.
Source:
Lancet Gastroenterol Hepatol
2023
Nov
; [e-pub].
(Abstract/FREE Full Text)
Empfohlen von
David H. Ilson, MD, PhD