Prospective randomized multicenter phase III trial comparing perioperative chemotherapy (FLOT protocol) to neoadjuvant chemoradiation (CROSS protocol) in patients with adenocarcinoma of the esophagus (ESOPEC trial).
Journal of Clinical Oncology, vol. 42, pp. LBA1
Abstract
LBA1 Background: The most effective multimodal approach for treatment of resectable locally advanced esophageal adenocarcinoma (EAC) is under debate. A prior ranking question is if neoadjuvant chemoradiation therapy or perioperative chemotherapy is superior. ESOPEC (NCT02509286) is a multicenter prospective randomized trial comparing neoadjuvant CROSS (41.4Gy plus carboplatin/paclitaxel) followed by surgery versus perioperative FLOT (5-FU/ leucovorin/oxaliplatin/docetaxel) and surgery for the curative treatment of EAC. Methods: Patients with cT1 cN+ cM0 or cT2-4a cNany cM0 resectable EAC were eligible. The primary endpoint is overall survival (OS; 90% power; hazard ratio [HR] 0.645, 218 events needed; one sided significance level of 2.5%). Analysis is by intention-to-treat in all randomized patients. The effect of treatment on OS is estimated using Cox regression stratified by study site, and including N stage (N0, N+), and age as covariates. Results: Between Feb 2016 and Apr 2020, 438 patients from 25 sites in Germany were randomly assigned to two treatment groups (221 FLOT; 217 CROSS). Baseline characteristics (male sex 89.3%, median age 63 [range 30-86], cT3/4 80.5%; cN+ 79.7%) were well balanced between both arms. Neoadjuvant treatment was started in 403 patients (207 FLOT; 196 CROSS). Surgery was done in 371 patients (191 FLOT; 180 CROSS). R0 resection was achieved in 351 patients (180 FLOT; 171 CROSS). 90 days postsurgical mortality was 4.3% (3.2% FLOT; 5.6% CROSS). After a median follow up of 55 months, 218 patients had died (97 FLOT; 121 CROSS). Median OS was 66 (95% CI 36 – not estimable) months in the FLOT arm, and 37 (95% CI 28 – 43) months in the CROSS arm. The 3-year OS rates were 57.4% (95% CI 50.1 – 64.0%) for FLOT and 50.7% (95% CI 43.5 – 57.5%) for CROSS (HR 0.70, 95% CI 0.53-0.92, p=0.012). In 359 patients with available tumor regression status, pathological complete response was achieved in 35 (19.3%, 95%-CI 13.9 – 25.9%) in FLOT and in 24 (13.5%, 95%-CI 8.8 – 19.4%) in CROSS. Conclusions: Perioperative FLOT improves survival in resectable EAC compared to neoadjuvant CROSS. Funding: The trial was funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation), project number 264590883. Clinical trial information: NCT02509286 .
Authors 20
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Affiliation as printed
University of Bielefeld, Bielefeld, Germany
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Affiliation as printed
Medical University of Graz, Department of Radiation Oncology, Graz, Austria
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University Hospital Leipzig · Leipzig University
Affiliation as printed
University of Leipzig Medical Center, Comprehensive Cancer Center Central Germany, Department of Medicine, Leipzig, Germany
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University of Freiburg · University Medical Center Freiburg
Affiliation as printed
Clinical Trials Unit Freiburg, Medical Center, University of Freiburg, Freiburg, Germany
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University Hospital Schleswig-Holstein
Affiliation as printed
Department of Surgery, University Medical Center Schleswig-Holstein, Luebeck, Luebeck, Germany
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Affiliation as printed
Department of Hematology and Oncology, University Hospital Aachen, Aachen, Germany
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Technische Universität Dresden · University Hospital Carl Gustav Carus
Affiliation as printed
University Hospital Carl Gustav Carus and Technische Universitat Dresden, Dresden, Germany
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University Hospital Schleswig-Holstein
Affiliation as printed
Department of Surgery, University Medical Center Schleswig-Holstein, Luebeck, Germany
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Affiliation as printed
Department of Surgery, University Hospital Magdeburg, Magdeburg, Germany
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Affiliation as printed
Department of Surgery, Klinikum Dortmund, Dortmund, Germany
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Affiliation as printed
Sana Klinikum Offenbach, Department of Hematology and Oncology, Offenbach Am Main, Germany
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University of Cologne · University Hospital Cologne
Affiliation as printed
Department of General, Visceral, Cancer and Transplantation Surgery, University Hospital of Cologne, Cologne, Germany
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University of Würzburg · Universitätsklinikum Würzburg
Affiliation as printed
Department of General, Visceral, Transplantation, Vascular and Pediatric Surgery, University Hospital, University of Wuerzburg, Wuerzburg, Germany
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University Hospital Schleswig-Holstein
Affiliation as printed
Department of General, Visceral, Thoracic, Transplantation, and Pediatric Surgery, UKSH Campus Kiel, Kiel, Germany
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Affiliation as printed
Department of General and Visceral Surgery, University Medical Center Goettingen, Goettingen, Germany
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Ruhr University Bochum · Johannes Wesling Klinikum Minden
Affiliation as printed
Department of Hematology, Oncology, Hemostaseology and Palliative Care, Johannes Wesling Medical Center Minden, Ruhr-University Bochum, Minden, Germany
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Affiliation as printed
Department of Visceral, Transplant, Thoracic and Vascular Surgery, University Hospital Leipzig, Leipzig, Germany
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University Medical Center Hamburg-Eppendorf
Affiliation as printed
Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
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University of Freiburg · University Medical Center Freiburg
Affiliation as printed
Department of General and Visceral Surgery, University Medical Center Freiburg, Freiburg, Germany
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University Medical Center of the Johannes Gutenberg University Mainz
Affiliation as printed
University Medical Center Mainz, Mainz, Germany
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