Window of Opportunity in Preserving Laryngeal Function Trial

Currently, for patients with locally advanced laryngeal or hypopharyngeal squamous cell carcinoma (SCC), there is the option of total laryngectomy (TL) followed by adjuvant pathology driven therapy (RT or CRT) or an organ preservation approach. Total laryngectomy is a particularly morbid surgery, leaving a patient breathing through the neck for the rest of their life. In recent years however, upfront total laryngectomy with adjuvant RT has been in focus to growing concern of reduced overall survival rates in advanced laryngeal and hypopharyngeal SCC, particularly in patients with T4 disease. As such, upfront TL with adjuvant RT or CRT is typical, with organ preservation protocols more controversial, for T4 LSCC specifically. This trial provides neoadjuvant (chemo)immunotherapy (induction regimen of platinum (carboplatin or cisplatin), paclitaxel, and toripalimab) allowing for a novel approach to patient bioselection for the treatment of laryngeal cancer. Toripalimab is approved in combination with cisplatin and gemcitabine for the first-line treatment of patients with recurrent and/or metastatic nasopharyngeal carcinoma and has shown to significantly improved PFS and OS when combined with cisplatin and gemcitabine. Patients who show response to neoadjuvant therapy in laryngeal cancer have been shown to have 1) a better survival than patients who do not respond and 2) respond better to nonsurgical therapy. The addition of immunotherapy to chemotherapy has the potential to improve the response rate to neoadjuvant therapy, decrease the number of patients who require total laryngectomy as their primary treatment, and to improve the survival of patients with this highly morbid disease.