Neoadjuvant chemotherapy combined with PD-1 inhibitor for laryngeal preservation in locally advanced hypopharyngeal squamous cell carcinoma: A single-arm, phase II clinical trial.

e18035 Background: Neoadjuvant chemotherapy (NCT) combination with PD-1 inhibitor has a significant efficacy and approved indications in the first-line treatment of R/M head and neck squamous cell carcinoma (HNSCC), but the efficacy of the combination therapy in locally advanced hypopharyngeal squamous cell carcinoma (HPSCC) remains unexplored. This study aimed to explore the efficacy and safety of NCT with PD-1 inhibitor for laryngeal preservation in patients with HPSCC. Methods: Patients with cT1N1-3M0 or cT2-3N0-3M0 (AJCC 8th) were eligible after multidisciplinary team (MDT) discussion. All patients received 2 cycles of intravenous docetaxel (60mg/m 2 on d1), cisplatin (60mg/m 2 on d1), fluorouracil (600mg/m2 per day as a continuous 120h infusion on d1-5) and toripalimab (240mg on d1) every 21 days. And the MDT underwent efficacy evaluation according to RECIST 1.1. Patients with complete response (CR)/partial response (PR) of the primary lesion(P) and no progressive disease (PD) in neck lymph nodes (LN) received definitive radiotherapy (RT) combined with toripalimab. Patients with stable disease (SD)/PD of P and no PD in LN or with PD in LN underwent surgery. Patients completed the third cycle of neoadjuvant therapy(NAT) before RT or surgery. The primary endpoint was the CR rate at 3 months (3m-CR) after NAT and definitive RT, and the secondary endpoints were the objective response rate (ORR) of NAT, laryngeal preservation rate, and adverse effects(AE). The sample size was calculated by the Simon-II-stage method: 27 patients in first stage (if ≥9 patients got 3m-CR, second stage started) , and a cumulative total of 81 patients in second stage. Results: From October 2020 to August 2023, 23 patients (median age:59, range:51-69, male:100%, stage II/III/IVA/IVB:4.3%/4.3%/26.1%/65.2%) were enrolled. After NAT, the ORR of primary tumor was 78.3% (18/23, including 2 CR), the ORR of lymph node was 65.2%% (15/23, including 9 CR), and the overall ORR was 70.0% (16/23). Fifteen patients received non-surgical treatment after NAT, and 8 patients underwent surgery (6 underwent laryngeal preservation surgery). At 3 months after RT or surgery, 18 patients completed evaluation. The CR rate was 77.8%, and the laryngeal preservation rate was 88.9%. In 13 evaluable patients who received NAT followed by definitive RT, 10 patients (76.9%) had an overall response of 3m-CR. During the NAT, 43.5% (10/23) of patients experienced grade 3-4 AEs, with grade 3-4 leukopenia or neutropenia in 30.4% (7/23) and grade 3 immune enteritis in 13.0% (3/23). Conclusions: NCT combination with PD-1 inhibitor may improve the ORR of HPSCC, potentially further increasing the laryngeal preservation rate, with manageable treatment-related AEs. The study results are pending publication after completion of the enrollment. Clinical trial information: NCT04624308 .