ESOPEC - ESOFAGO - CROSS X FLOT

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LBA1 Plenary Session
Prospective randomized multicenter phase III trial comparing perioperative che-
motherapy (FLOT protocol) to neoadjuvant chemoradiation (CROSS protocol) in
patients with adenocarcinoma of the esophagus (ESOPEC trial).
Jens Hoeppner, Thomas Brunner, Florian Lordick, Claudia Schmoor, Birte Kulemann, Ulf Peter Neumann, Gunnar Folprecht, Tobias Keck, Frank Benedix,
Maximilan Schmeding, Ernst Reitsamer, Christiane J. Bruns, Johan F. Lock, Benedikt Reichert, Michael Ghadimi, Kai Wille, Ines Gockel, Jakob R. Izbicki, Stefan Utzolino,
Peter Philipp Grimminger; University of Bielefeld, Bielefeld, Germany; Medical University of Graz, Department of Radiation Oncology, Graz, Austria; University of Leipzig
Medical Center, Comprehensive Cancer Center Central Germany, Department of Medicine, Leipzig, Germany; Clinical Trials Unit Freiburg, Medical Center, University of
Freiburg, Freiburg, Germany; Department of Surgery, University Medical Center Schleswig-Holstein, Luebeck, Luebeck, Germany; Department of Hematology and Oncology,
University Hospital Aachen, Aachen, Germany; University Hospital Carl Gustav Carus and Technische Universitat Dresden, Dresden, Germany; Department of Surgery,
University Medical Center Schleswig-Holstein, Luebeck, Germany; Department of Surgery, University Hospital Magdeburg, Magdeburg, Germany; Department of Surgery,
Klinikum Dortmund, Dortmund, Germany; Sana Klinikum Offenbach, Department of Hematology and Oncology, Offenbach Am Main, Germany; Department of General,
Visceral, Cancer and Transplantation Surgery, University Hospital of Cologne, Cologne, Germany; Department of General, Visceral, Transplantation, Vascular and Pediatric
Surgery, University Hospital, University of Wuerzburg, Wuerzburg, Germany; Department of General, Visceral, Thoracic, Transplantation, and Pediatric Surgery, UKSH
Campus Kiel, Kiel, Germany; Department of General and Visceral Surgery, University Medical Center Goettingen, Goettingen, Germany; Department of Hematology,
Oncology, Hemostaseology and Palliative Care, JohannesWesling Medical Center Minden, Ruhr-University Bochum, Minden, Germany; Department of Visceral, Transplant,
Thoracic and Vascular Surgery, University Hospital Leipzig, Leipzig, Germany; Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-
Eppendorf, Hamburg, Germany; Department of General and Visceral Surgery, University Medical Center Freiburg, Freiburg, Germany; University Medical Center Mainz,
Mainz, Germany
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; 196CROSS). Surgerywas done in 371 patients (191 FLOT; 180 CROSS).
R0 resectionwas achieved in 351 patients (180 FLOT; 171 CROSS). 90 days postsurgicalmortality
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 Forschungs-
gemeinschaft (DFG, German Research Foundation), project number 264590883. Clinical trial
information: NCT02509286. Research Sponsor: DFG.
GASTROINTESTINAL CANCER—GASTROESOPHAGEAL, PANCREATIC, AND HEPATOBILIARY
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http://www.clinicaltrials.gov/ct2/show/NCT02509286
http://crossmark.crossref.org/dialog/?doi=10.1200%2FJCO.2024.42.17_suppl.LBA1&domain=pdf&date_stamp=2024-06-05