Chemoradiation therapy With Cisplatin Versus Cetuximab in Patients With Locoregionally Advanced Head and Neck Squamous Cell Cancer—Mature Results of the ARTSCAN III Trial
Maria Gebre‐Medhin, Gabriel Adrian, Per Engström, Hedda Haugen Cange, Lalle Hammarstedt‐Nordenvall, Johan Reizenstein, Eva Brun, Jan Nyman, Edvard Abel, Signe Friesland, Helena Sjödin, Karin Söderkvist, Marcus Thomasson, Björn Zackrisson, Per Nilsson
Abstract
PURPOSE: The study investigated curative radiation therapy (RT) plus cisplatin versus RT plus cetuximab in patients with locoregionally advanced head and neck squamous cell carcinoma (HNSCC). METHODS AND MATERIALS: during RT. Primary endpoint was overall survival (OS), evaluated by adjusted Cox regression analysis. Secondary endpoints were locoregional control, pattern of failure, morbidity, quality of life (QL), and comparisons between dose-escalated RT and standard-dose RT in T3-T4 tumors. RESULTS: Following an unplanned interim analysis, patient inclusion was prematurely closed. The intention-to-treat population included 291 patients, 76% of whom had p16-positive oropharyngeal cancer. Median follow-up was 7.5 years for OS and 5.3 years for treatment efficacy. Five-year OS was 82% (95% confidence interval [CI], 76-89) in the RT plus cisplatin group compared with 71% (95% CI, 64-79) in the RT plus cetuximab group (log-rank P = .019). Adjusted hazard ratios for OS, locoregional failure, and distant failure were 1.66 (95% CI, 1.08-2.56; P = .021), 2.24 (95% CI, 1.25-4.02; P = .007), and 1.44 (95% CI, 0.67-3.09; P = .34), respectively, for patients treated with concomitant cetuximab versus cisplatin. Although potentially affected by the early termination of patient inclusion, no improvement in local control was found in patients with T3-T4 tumors receiving RT dose escalation (adjusted HR, 0.63; 95% CI, 0.30-1.34; P = .23). Late morbidity and QL were similar between the treatment groups. CONCLUSIONS: The study showed inferior treatment outcomes for cetuximab compared with cisplatin concurrent with RT. Cisplatin remains standard concomitant treatment for locoregionally advanced HNSCC.