Perioperative FLOT Improves Survival in Resectable Esophageal Carcinoma

OS at 3 years was 57.4% (n = 221; 95% CI, 50.1-64.0) for the perioperative FLOT group, compared with 50.7% (n = 217; 95% CI, 43.5-57.5) for the preoperative chemoradiotherapy group.

Results of the ESOPEC trial (NCT02509286) showed the combination of ­­perioperative chemotherapy using fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) with surgery to be more effective overall than preoperative chemoradiotherapy plus surgery for patients with resectable esophageal carcinoma.

Despite these benefits, the researchers noted that FLOT exhibited more adverse events (AEs).

“The current trial showed that overall survival was better with FLOT than with preoperative chemoradiotherapy among patients with resectable esophageal adenocarcinoma, including those with a clinical lymph-node stage of cN+ and those with a clinical tumor stage of cT3 or cT4, who made up most of the trial population,” wrote the researchers in an article in The New England Journal of Medicine.

Overall survival (OS) at 3 years was higher for the perioperative FLOT group (n = 221) at 57.4% (95% CI, 50.1%-64.0%) compared with 50.7% (95% CI, 43.5%-57.5%) for the preoperative chemoradiotherapy group (n = 217), with a median follow-up of 55 months. The hazard ratio for death was 0.70 (95% CI, 0.53-.92; P = .01).

The FLOT group continued to see improved results at 5 years, at which its OS was 50.6% (95% CI, 43.2%-57.6%) vs 38.7% (95% CI, 31.5%-45.9%) in the preoperative chemoradiotherapy group. Of note, median OS in the FLOT arm was 66 months (95% CI, 36-not estimable [NE] compared with 37 months (95% CI, 28-43) in the chemoradiotherapy group.

At 3 years, progression-free survival (PFS) in the FLOT and chemoradiotherapy groups was 51.6% (95% CI, 44.3%-58.4%) compared to 35.0% (95% CI, 28.4%-41.7%), respectively (HR for disease progression or death = 0.66; 95% CI, 0.51-0.85).

Participants in the phase 3, multicenter, randomized trial included 438 patients with resectable esophageal adenocarcinoma. In the FLOT arm, 70.5% of patients had a clinical tumor stage of cT3 and 77.8% had a clinical lymph node stage of cN+. Similarly, 77.3% of patients in the chemoradiotherapy group had a clinical tumor stage of cT3 and 81.6% had a clinical lymph node stage of cN+.

By the 90-day mark, The Kaplan-Meier estimate for mortality was 3.1% in the FLOT group and 5.6% in the chemoradiotherapy group. Disease progression or any-cause death occurred in 107 patients in the FLOT arm and 137 in the chemoradiotherapy arm.

There were 89 occurrences of tumor progression in the perioperative FLOT group and 118 in the preoperative chemotherapy group. Of those patients, 1 patient in the FLOT group and 11 in the chemoradiotherapy group had distant metastases detected before treatment.

Grade 3 or worse AEs occurred in 50.0% of those treated with preoperative chemoradiotherapy and 58.0% of those treated with FLOT. Serious AEs were reported in 41.8% of patients in the chemoradiotherapy group and in 47.3% of those in the FLOT group.

The most common series AE, occurring in at least 5% of patients, was pneumonia, reported in 5.3% of patients in the FLOT group and 8.7% of those in the chemoradiotherapy group. For patients treated with FLOT, the most common grade 3 or higher AEs besides pneumonia were neutropenia (19.8%) diarrhea (6.8%), and leukopenia (9.7%). The most common grade 3 or higher AE besides pneumonia was leukopenia (9.7%) for the chemoradiotherapy group.

“Whether de-escalation to a chemotherapy doublet or a switch to preoperative chemoradiotherapy is the preferred approach in patients to whom FLOT cannot be given because of coexisting conditions or in those with FLOT-related adverse events remains a question that our trial cannot answer,” the study authors concluded.

Reference

Hoeppner J, Brunner T, Schmoor C, et al. Perioperative chemotherapy or preoperative chemoradiotherapy in esophageal cancer. N Engl J Med. 2025;392:323-335. doi:10.1056/NEJMoa2409408