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

Rades, Dirk; Bartscht, Tobias; Hunold, Peter; Schmidberger, Heinz; König, Laila; Debus, Jurgen; Belka, Claus; Homann, Nils; Spillner, Patrick; Petersen, Cordula; Kuhnt, Thomas; Fietkau, Rainer; Ridwelski, Karsten; Karcher-Kilian, Kerstin; Kranich, Anne; Maennikkoe, Sofia; Schild, Steven E.; Maderer, Annett und Moehler, Markus (2020): Radiochemotherapy with or without cetuximab for unresectable esophageal cancer: final results of a randomized phase 2 trial (LEOPARD-2). In: Strahlentherapie und Onkologie, Bd. 196, Nr. 9: S. 795-804

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 & x202f;= H-0), and promising if the lower limit of the 95% confidence interval was >45%. If that lower limit was >40%, H(0)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%);H(0)was rejected. Median OS was 49.1 vs. 24.1 months (p & x202f;= 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 & x202f;= 0.262). Twenty-six and 27 patients, respectively, experienced at least one toxicity grade >= 3 (p & x202f;= 0.573). A significant difference was found for grade >= 3 allergic reactions (12.5% vs. 0%,p & x202f;= 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.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 0179-7158
• Sprache: Englisch