Efficacy and safety of neoadjuvant immune checkpoint inhibitors combined with chemotherapy in locally advanced hypopharyngeal squamous cell carcinoma: a retrospective analysis.

OBJECTIVE: To evaluate the efficacy and safety of neoadjuvant PD-1 inhibitor combined with chemotherapy (nab-paclitaxel + cisplatin) in patients with locally advanced hypopharyngeal squamous cell carcinoma. METHODS: A retrospective analysis was conducted on 75 patients with locally advanced (stage III-IVA) hypopharyngeal cancer diagnosed at the First Affiliated Hospital of Xiamen University between January 2021 and May 2023. All patients received at least 2 cycles of neoadjuvant immunochemotherapy followed by radical surgery and adjuvant radiotherapy. Objective response rate (ORR), major pathological response (MPR), pathological complete response (pCR), larynx-preserving surgery rate, progression-free survival (PFS), and safety were evaluated. RESULTS: Among 75 patients, the ORR was 77.3% (58/75), MPR rate was 78.7% (59/75), standard pCR rate (primary + lymph nodes) was 17.3% (13/75), primary tumor pCR rate was 26.7% (20/75), and larynx-preserving surgery rate was 86.7% (65/75). With a median follow-up of 26 months, the 12-month and 24-month overall survival rates were 93.3% and 76.0%, respectively, and the PFS rates were 92.0% and 76.0%, respectively. The MPR group demonstrated significantly superior PFS compared to the non-MPR group (HR = 0.052, 95% CI: 0.019-0.140, P < 0.001), with 24-month PFS rates of 89.7% and 12.5%, respectively. The ORR group also showed significantly superior PFS compared to the non-ORR group (HR = 0.29, 95% CI: 0.13-0.66, P = 0.003), with 24-month PFS rates of 86.2% and 41.2%, respectively. Concordance between radiological and pathological assessments was moderate (κ=0.417, P < 0.001). The safety profile was favorable, with no grade 3-5 treatment-related adverse events observed. CONCLUSION: Neoadjuvant PD-1 inhibitor combined with chemotherapy induces significant radiological and pathological responses in patients with locally advanced hypopharyngeal cancer, effectively improving larynx-preserving surgery rate and progression-free survival with a favorable safety profile. Pathological assessment (particularly MPR) may provide complementary prognostic information to radiological assessment.This regimen demonstrates promising short-term efficacy and larynx preservation benefits, warranting further prospective validation.