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

Rades D, Bartscht T, Hunold P, Schmidberger H, König L, Debus J, Belka C, Homann N, Spillner P, Petersen C, Kuhnt T, Fietkau R, Ridwelski K, Karcher-Kilian K, Kranich A, Männikkö S, Schild SE, Maderer A, Moehler M (2020)

Publication Type: Journal article

Publication year: 2020

Journal

Strahlentherapie und Onkologie Urban & Vogel

DOI: 10.1007/s00066-020-01646-4

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.

Authors with CRIS profile

Rainer Fietkau Lehrstuhl für Strahlentherapie

Involved external institutions

Universität zu Lübeck DE Germany (DE) Eberhard Karls Universität Tübingen DE Germany (DE) Universitätsklinikum Leipzig DE Germany (DE) Mayo Clinic in Arizona US United States (USA) (US) Ruprecht-Karls-Universität Heidelberg DE Germany (DE) Johannes Gutenberg-Universität Mainz (JGU) DE Germany (DE) Universitätsklinikum Hamburg-Eppendorf (UKE) DE Germany (DE) Klinikum Wolfsburg DE Germany (DE) Ludwig-Maximilians-Universität (LMU) DE Germany (DE) Forendo Pharma Ltd. NO Norway (NO) Klinikum Magdeburg DE Germany (DE)

How to cite

APA:

Rades, D., Bartscht, T., Hunold, P., Schmidberger, H., König, L., Debus, J.,... Moehler, M. (2020). Radiochemotherapy with or without cetuximab for unresectable esophageal cancer: final results of a randomized phase 2 trial (LEOPARD-2). Strahlentherapie und Onkologie. https://doi.org/10.1007/s00066-020-01646-4

MLA:

Rades, Dirk, et al. "Radiochemotherapy with or without cetuximab for unresectable esophageal cancer: final results of a randomized phase 2 trial (LEOPARD-2)." Strahlentherapie und Onkologie (2020).

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