Larynx preservation clinical trial design: summary of key recommendations of a consensus panel

An international consensus panel was convened to develop guidelines for the conduct of phase III clinical trials of larynx preservation in patients with locally advanced laryngeal and hypopharyngeal cancer. According to their recommendations, future trial populations should include patients with T2 or T3 laryngeal or hypopharyngeal squamous cell carcinoma not considered for partial laryngectomy and should exclude those with laryngeal dysfunction or aged >70 years. Baseline and post-treatment functional assessments should include speech and swallowing evaluations. Furthermore, voice should be routinely assessed with a simple, validated instrument. Regarding endpoints, the primary endpoint should capture survival and function. As a result, the panel created a new endpoint of laryngoesophageal dysfunction (LED)-free survival, which includes the events of death, local relapse, total or partial laryngectomy, tracheotomy at ≥2 years, or feeding tube at ≥2 years. Recommended secondary endpoints are freedom from LED, overall survival, progression-free survival, locoregional control, time to tracheotomy, time to laryngectomy, time to discontinuation of feeding tube, and quality of life/patient-reported outcomes. Future exploratory correlative biomarker studies should include epidermal growth factor receptor, excision repair cross-complementation group 1 gene, E-cadherin and β-catenin, epiregulin and amphiregulin, and TP53 mutation. Revised trial designs in several key areas are needed to advance the study of larynx preservation. With consistent methodologies, clinical trials can more effectively evaluate and quantify the therapeutic benefit of novel treatment options for patients with locally advanced laryngeal and hypopharyngeal cancer.