Chemoradiation therapy With Cisplatin Versus Cetuximab in Patients With Locoregionally Advanced Head and Neck Squamous Cell Cancer-Mature Results of the ARTSCAN III Trial

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: This was a Swedish multicenter randomized phase 3 study. Included patients were randomized 1:1. Patients with T3-T4 tumors underwent a second randomization 1:1 between a final RT dose of 68.0 and 73.1 Gy to the primary tumor. Cisplatin dosage was 40 mg/m²/wk during RT. Cetuximab was administered with a loading dose of 400 mg/m² 1 week before start of RT, followed by weekly doses of 250 mg/m² 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.