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Bending the Curve Trial by Trial
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ESOPEC

Perioperative chemotherapy or preoperative chemoradiotherapy in esophageal cancer (ESOPEC)

Phase 3N = 438NCT02509286

Population
Resectable oesophageal adenocarcinoma (the design paper states oesophageal and junctional adenocarcinoma)
Design
Multicentre phase 3 trial, patients assigned 1:1 to perioperative chemotherapy with FLOT (fluorouracil, leucovorin, oxaliplatin, docetaxel) plus surgery, or preoperative chemoradiotherapy (41.4 Gy with carboplatin and paclitaxel) plus surgery. Eligible: cT1 cN+, cT2-4a cN+ or cT2-4a cN0 without metastases. 438 patients assigned from February 2016 to April 2020. Primary endpoint overall survival.
Primary endpoint
OS
Arms
  • Perioperative FLOT (experimental, n = 221): Perioperative chemotherapy with FLOT plus surgery
  • Preoperative chemoradiotherapy (CROSS) (control, n = 217): Preoperative carboplatin and paclitaxel with 41.4 Gy radiotherapy, then surgery
People
Hoeppner J
OSHR 0.70 (95% CI 0.53–0.92)Δ 36-month OS+6.7 pointsPFSHR 0.66 (95% CI 0.51–0.85)Δ 36-month PFS+16.6 pointsRFSHR 0.67 (95% CI 0.51–0.89)Δ 36-month RFS+15.5 points
Show the numbers
Results reported for ESOPEC
EndpointAnalysisPerioperative FLOTPreoperative chemoradiotherapy (CROSS)Effect
OSAll assigned patients (221 vs 217)primarymedian follow-up 55 monthsHoeppner 202557.4% at 3 y (50.1–64.0%)50.7% at 3 y (43.5–57.5%)HR 0.70 (95% CI 0.53–0.92)P=0.01Median overall survival is not given in the abstract. Mortality 90 days after surgery: 3.1% with FLOT vs 5.6% with chemoradiotherapy. Grade 3 or higher adverse events among patients who started assigned treatment: 58.0% (120 of 207) vs 50.0% (98 of 196).
PFSAll assigned patients (221 vs 217)primarymedian follow-up 55 monthsHoeppner 202551.6% at 3 y (44.3–58.4%)35% at 3 y (28.4–41.7%)HR 0.66 (95% CI 0.51–0.85)Secondary endpoint.
RFSPatients who underwent resection (192 of 221 FLOT; 179 of 217 CROSS)long term-updatemedian follow-up 56 monthsHoeppner 202554.5% at 3 y39% at 3 yHR 0.67 (95% CI 0.51–0.89)P=0.005Recurrence-pattern analysis. Locoregional recurrence: 39 vs 32 patients (3-year cumulative incidence 20.2% vs 17.4%; HR 1.00, 95% CI 0.62 to 1.61; P=.99). Distant recurrence: 64 vs 89 patients (3-year cumulative incidence 31.5% vs 47.2%; HR 0.59, 95% CI 0.43 to 0.82; P=.002).
Results reported for ESOPEC
EndpointAnalysisPerioperative FLOTPreoperative chemoradiotherapy (CROSS)Effect
OSAll assigned patients (221 vs 217)primarymedian follow-up 55 monthsHoeppner 202557.4% at 3 y (50.1–64.0%)50.7% at 3 y (43.5–57.5%)HR 0.70 (95% CI 0.53–0.92)P=0.01Median overall survival is not given in the abstract. Mortality 90 days after surgery: 3.1% with FLOT vs 5.6% with chemoradiotherapy. Grade 3 or higher adverse events among patients who started assigned treatment: 58.0% (120 of 207) vs 50.0% (98 of 196).
PFSAll assigned patients (221 vs 217)primarymedian follow-up 55 monthsHoeppner 202551.6% at 3 y (44.3–58.4%)35% at 3 y (28.4–41.7%)HR 0.66 (95% CI 0.51–0.85)Secondary endpoint.
RFSPatients who underwent resection (192 of 221 FLOT; 179 of 217 CROSS)long term-updatemedian follow-up 56 monthsHoeppner 202554.5% at 3 y39% at 3 yHR 0.67 (95% CI 0.51–0.89)P=0.005Recurrence-pattern analysis. Locoregional recurrence: 39 vs 32 patients (3-year cumulative incidence 20.2% vs 17.4%; HR 1.00, 95% CI 0.62 to 1.61; P=.99). Distant recurrence: 64 vs 89 patients (3-year cumulative incidence 31.5% vs 47.2%; HR 0.59, 95% CI 0.43 to 0.82; P=.002).
Hazard ratio (95% CI) by endpoint. Values below 1 favour the experimental arm.
OSPFSRFS0.512◀ experimentalcontrol ▶
Data table
EndpointHR95% CI
OS0.70.53–0.92
PFS0.660.51–0.85
RFS0.670.51–0.89
Primary publication: Hoeppner J, Brunner T, Schmoor C, Bronsert P, Kulemann B, Claus R, et al. Perioperative Chemotherapy or Preoperative Chemoradiotherapy in Esophageal Cancer. N Engl J Med. 2025;392(4):323-335. PubMedDOI

Appears in

Sources

  1. Hoeppner J, Brunner T, Schmoor C, Bronsert P, Kulemann B, Claus R, et al. Perioperative Chemotherapy or Preoperative Chemoradiotherapy in Esophageal Cancer. N Engl J Med. 2025;392(4):323-335.

    PubMedDOI

  2. Hoeppner J, Schmoor C, Brunner T, Bronsert P, Plum PS, Nimczewski F, et al. Recurrence Patterns of Esophageal Adenocarcinoma in the Phase III ESOPEC Trial Comparing Perioperative Chemotherapy With Preoperative Chemoradiotherapy. J Clin Oncol. 2025;43(32):3451-3456.

    PubMedDOI