Patients with nonmetastatic esophageal cancer who received FLOT chemotherapy achieved a 3-year OS rate of 61.1% in an analysis of the phase 3 ESOPEC trial.
Perioperative chemotherapy with fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) chemotherapy demonstrated improved survival and better systemic tumor control, reducing distant tumor recurrences, when compared with carboplatin and paclitaxel (CROSS), in patients with nonmetastatic esophageal adenocarcinoma, as shown in results from the phase 3 ESOPEC trial (NCT02509286) published in the Journal of Clinical Oncology.1
With a median follow-up of 56 months, the 3-year overall survival (OS) rates were 61.1% in the FLOT group vs 55.9% in the CROSS group (HR, 0.71; 95% CI, 0.53-0.97; P = .030). Eighty and 98 patients, in the FLOT and CROSS groups, respectively, who underwent tumor resection died; 65 and 81 patients died with tumor recurrence, and 15 and 7 died without evidence of recurrence.
The 3-year cumulative incidence rates of death with recurrence were 32.3% in the FLOT group and 34.9% in the CROSS group (HR, 0.70; 95% CI, 0.50-0.98; P = .040); the 3-year cumulative incidence rates of death without evidence of recurrence were 6.6% and 9.2%, respectively (HR, 0.79; 95% CI, 0.38-1.65; P = .53).
The 3-year recurrence-free survival (RFS) rate was 54.5% in the FLOT group vs 39.0% in the CROSS group (HR, 0.67; 95% CI, 0.51-0.89; P = .005); the median RFS was 47 months (95% CI, 28-not estimable) vs 19 months (95% CI, 15-27), respectively.
The 3-year cumulative incidence of locoregional recurrence was 20.2% in the FLOT group and 17.4% in the CROSS group (HR, 1.00; 95% CI, 0.62-1.61; P = .99); of these patients, locoregional recurrence was evident in 19 vs 15 patients, respectively (HR, 1.03; 95% CI, 0.51-2.06; P = .94), and regional recurrence was evident in 29 vs 27 patients (HR, 0.89; 95% CI, 0.52-1.52; P = .68). Further, distant recurrence occurred with a 3-year cumulative incidence rate of 31.5% in the FLOT group and 47.2% in the CROSS group (HR, 0.59; 95% CI, 0.43-0.82; P = .002).
Common sites of recurrence such as distant lymphatic (HR, 0.60; 95% CI, 0.34 to 1.05; P = .074), hematogenous (HR, 0.59; 95% CI, 0.37 to 0.92; P = .021), and pleural and peritoneal (HR, 0.63; 95% CI, 0.36-1.09; P = .098) metastases, were less common with FLOT compared with CROSS. Distant recurrences occurred without simultaneous local or regional recurrences, with a 3-year cumulative incidence of 20.4% vs 34.4%, respectively (HR, 0.53; 95% CI, 0.36-0.79; P = .002).
“These results indicate that CROSS had insufficient effects on distant recurrence compared with FLOT and that the increased mortality is a consequence of lower systemic antitumor efficacy,” wrote lead study author Florian Lordick, MD, of the department of Medicine II, at University Cancer Center Leipzig, Cancer Center Central Germany, University of Leipzig medical Center, in Leipzig, Germany, and coauthors, in the analysis.1“In conclusion, perioperative chemotherapy with FLOT and preoperative chemoradiotherapy with CROSS resulted in comparable locoregional recurrence rates and significantly lower distant recurrence rates in favor of FLOT.”
This analysis included a total of 435 patients who were randomly assigned to receive either FLOT and surgery (n = 221) or CROSS and surgery (n = 217). In this analysis, eligible patients had cT1 cN+ cM0 or cT2 to cT4a cNany cM0 EAC, and underwent tumor resection in the ESOPEC trial.
Inclusion criteria for the ESOPEC trial included histologically verified adenocarcinoma of the esophagus; an age of 18 years or more; no prior abdominal or thoracic radiotherapy; an ECOG performance status from 0 to 2; and adequate cardiac, bone marrow, respiratory, renal, and liver function.2
Exclusion criteria included tumors of squamous or other non-adenocarcinoma histology; advanced inoperable or metastatic esophageal adenocarcinoma; prior chemotherapy for cancer; clinically significant cardiac disease; clinically significant lung disease; gastric carcinoma; and peripheral neuropathy of grade 2 and higher.
The primary end point of this analysis was OS. Secondary end points included cause-specific mortality, RFS, local recurrence, regional recurrence, and distant recurrence.
The investigators noted undetected distant metastases as a limitation of the study because PET/CT and staging laparoscopy were not mandatory, and thus not performed for all before study inclusion.
References
- Hoeppner J, Schmoor C, Brunner T, et al. Recurrence patterns of esophageal adenocarcinoma in the phase III ESOPEC trial comparing perioperative chemotherapy with preoperative chemoradiotherapy. J Clin Oncol. Published online July 9, 2025. doi:10.1200/JCO-25-00948
- Perioperative chemotherapy compared to neoadjuvant chemoradiation in patients with adenocarcinoma of the esophagus (ESOPEC). ClinicalTrials.gov. Updated May 8, 2024. Accessed July 16, 2025. https://tinyurl.com/2s48jvja