本研究的目的是评估诱导化疗联合PD-1抑制剂保留喉治疗局部晚期喉癌和下咽癌的疗效、毒性和潜在作用。这是一项单臂II期研究。组织病理学证实、可切除的局部晚期喉/下咽鳞状细胞癌且 ECOG PS 0-1 的患者符合资格。给予3周期诱导化疗（紫杉醇175mg/m2·d1、顺铂25mg/m2·d1-3）联合PD-1抑制剂（特瑞普利单抗240mg·d0）。诱导化学免疫治疗后使用 RECIST 1·1 标准进行疗效评估。原发肿瘤完全/部分缓解的患者接受同步放化疗，然后接受特瑞普利单抗维持治疗。否则，患者被转诊接受手术，然后接受辅助（化学）放射治疗和特瑞普利单抗维持治疗。主要终点是放射后三个月的喉部保留率。共有 27 名患者入组。大多数病例表现出IV期疾病（81·5%），其中T4期占37·0%。 5 名患者因喉功能受损而接受了治疗前气管切开术。诱导化学免疫治疗总有效率85·2%。放射后三个月喉部保存率为88·9%。中位随访18·7个月，1年OS率、PFS率、喉保留率分别为84·7%、77·6%和88·7%。排除预处理气管切开术者，1年喉保存率为95·5%。探索性分析显示复发与缺氧和 M2 巨噬细胞相关基因的 RNA 特征富集相关。诱导特瑞普利单抗联合化疗在这组广泛局部晚期喉癌和下咽癌中提供了令人鼓舞的活性、有希望的喉部保留率和可接受的毒性。

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.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.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.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.