Induction Toripalimab And Chemotherapy For Organ Preservation In Locally Advanced Laryngeal And Hypopharyngeal Cancer: A Single-Arm Phase 2 Clinical Trial

Abstract Purpose: The aim of this study was to assess the efficacy, toxicities, and potential role of larynx preservation of induction chemotherapy combined with PD-1 inhibitor in locally advanced laryngeal and hypopharyngeal cancer. Methods: This is a single-arm phase II study. Patients with histopathologic confirmed, resectable locally advanced laryngeal/hypopharyngeal squamous cell carcinoma and ECOG PS 0-1 were eligible. Three cycles of induction chemotherapy (paclitaxel 175mg/m2 d1, cisplatin 25mg/m2 d1-3) combined with PD-1 inhibitor (toripalimab 240mg d0) were administered. Response assessment was performed after induction chemoimmunotherapy using RECIST 1·1 criteria. Patients with complete/partial response of primary tumor received concurrent chemoradiation, followed by maintenance therapy of toripalimab. Otherwise, patients were referred to surgery, followed by adjuvant (chemo)radiation, and maintenance therapy of toripalimab. The primary endpoint is larynx-preservation rate at three months post-radiation. Results: Twenty-seven patients were enrolled. Most cases exhibited stage IV disease (81·5%), with T4 representing 37·0%. Five patients underwent pretreatment tracheostomy due to impaired larynx function. Overall response rate of induction chemoimmunotherapy was 85·2%. At three months post-radiation, the larynx preservation rate was 88·9%. With a median follow-up of 18·7 months, 1-year OS rate, PFS rate, larynx preservation rate was 84·7%, 77·6% and 88·7%, respectively. When excluding those with pretreatment tracheostomy, 1-year larynx preservation rate was 95·5%. Exploratory analysis revealed relapse correlated with enrichment of RNA signature of hypoxia and M2 macrophages associated genes. Conclusions: Induction toripalimab combined with chemotherapy provided encouraging activity, promising larynx preservation rate and acceptable toxicity in this cohort of extensively locally advanced laryngeal and hypopharyngeal cancer.