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

Dirk Rades*, 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

*Corresponding author for this work


Purpose: To investigate the efficacy and toxicity of cetuximab when added to radiochemotherapy for unresectable esophageal cancer. Methods: This randomized phase 2 trial (, 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.

Original languageEnglish
JournalStrahlentherapie und Onkologie
Issue number9
Pages (from-to)795-804
Number of pages10
Publication statusPublished - 01.09.2020

Research Areas and Centers

  • Academic Focus: Biomedical Engineering


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