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Open Access 01-09-2020 | Esophageal Cancer | Original Article

Radiochemotherapy with or without cetuximab for unresectable esophageal cancer: final results of a randomized phase 2 trial (LEOPARD-2)

Authors: Dirk Rades, M.D., Tobias Bartscht, Peter Hunold, Heinz Schmidberger, Laila König, Jürgen Debus, Claus Belka, Nils Homann, Patrick Spillner, Cordula Petersen, Thomas Kuhnt, Rainer Fietkau, Karsten Ridwelski, Kerstin Karcher-Kilian, Anne Kranich, Sofia Männikkö, Steven E. Schild, Annett Maderer, Markus Moehler

Published in: Strahlentherapie und Onkologie | Issue 9/2020

Abstract

Purpose

To investigate the efficacy and toxicity of cetuximab when added to radiochemotherapy for unresectable esophageal cancer.

Methods

This randomized phase 2 trial (clinicaltrials.gov, identifier NCT01787006) compared radiochemotherapy plus cetuximab (arm A) to radiochemotherapy (arm B) for unresectable esophageal cancer. Primary objective was 2‑year overall survival (OS). Arm A was considered insufficiently active if 2‑year OS was ≤40% (null hypothesis = H₀), and promising if the lower limit of the 95% confidence interval was >45%. If that lower limit was >40%, H₀ was rejected. Secondary objectives included progression-free survival (PFS), locoregional control (LC), metastases-free survival (MFS), response, and toxicity. The study was terminated early after 74 patients; 68 patients were evaluable.

Results

Two-year OS was 71% in arm A (95% CI: 55–87%) vs. 53% in arm B (95% CI: 36–71%); H₀ was rejected. Median OS was 49.1 vs. 24.1 months (p = 0.147). Hazard ratio (HR) for death was 0.60 (95% CI: 0.30–1.21). At 2 years, PFS was 56% vs. 44%, LC 84% vs. 72%, and MFS 74% vs. 54%. HRs were 0.51 (0.25–1.04) for progression, 0.43 (0.13–1.40) for locoregional failure, and 0.43 (0.17–1.05) for distant metastasis. Overall response was 81% vs. 69% (p = 0.262). Twenty-six and 27 patients, respectively, experienced at least one toxicity grade ≥3 (p = 0.573). A significant difference was found for grade ≥3 allergic reactions (12.5% vs. 0%, p = 0.044).

Conclusion

Given the limitations of this trial, radiochemotherapy plus cetuximab was feasible. There was a trend towards improved PFS and MFS. Larger studies are required to better define the role of cetuximab for unresectable esophageal cancer.

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Title: Radiochemotherapy with or without cetuximab for unresectable esophageal cancer: final results of a randomized phase 2 trial (LEOPARD-2)
Authors: Dirk Rades, M.D.
Tobias Bartscht
Peter Hunold
Heinz Schmidberger
Laila König
Jürgen Debus
Claus Belka
Nils Homann
Patrick Spillner
Cordula Petersen
Thomas Kuhnt
Rainer Fietkau
Karsten Ridwelski
Kerstin Karcher-Kilian
Anne Kranich
Sofia Männikkö
Steven E. Schild
Annett Maderer
Markus Moehler
Publication date: 01-09-2020
Publisher: Springer Berlin Heidelberg
Keywords: Esophageal Cancer
Esophageal Cancer
Cetuximab
Published in: Strahlentherapie und Onkologie / Issue 9/2020
Print ISSN: 0179-7158
Electronic ISSN: 1439-099X
DOI: https://doi.org/10.1007/s00066-020-01646-4

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Radiochemotherapy with or without cetuximab for unresectable esophageal cancer: final results of a randomized phase 2 trial (LEOPARD-2)

Abstract

Purpose

Methods

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusion

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