Cetuximab in combination with immunotherapy and chemotherapy as preoperative induction therapy for locally advanced HNSCC: A retrospective study.

Abstract

e18027 Background: The survival of head and neck squamous cell carcinoma (HNSCC) patients has improved with the use of anti-epidermal growth factor receptor (EGFR) therapy and immunotherapy. However, the benefits and safety of preoperative induction therapy with the combination therapy for locally advanced HNSCC (LA-HNSCC) remain unclear. Methods: This is a retrospective analysis of the efficacy and safety of preoperative cetuximab combined with immunotherapy and chemotherapy in patients with LA-HNSCC treated during March 2023 to March 2025. Patients who had no previous drug treatment, received cetuximab + immunotherapy + chemotherapy before surgery were eligible. The primary endpoint was major pathological response (MPR) rate. Secondary endpoints included R0 resection rate, downstage migration rate, disease-free survival rate and safety. Results: 12 patients were included in the analysis (including 3 p16-negative oropharyngeal cancer, and 7 hypopharyngeal cancer). Most patients had stage IVA (3) or stage IVB (7) disease. Ten patients were treatment-naive, and 2 had recurrent disease after prior surgery. The combination drug regimen was cetuximab + PD-1 monoclonal antibody + chemotherapy (mainly taxanes + platinum-based drugs). Drug treatment was administered for 2-5 cycles, with a median of 3 cycles.Efficacy evaluation was performed after the completion of preoperative induction therapy. ORR (overall response rate) was 41.67%, and DCR (disease control rate) was 100%. 11 (91.67%) patients achieved R0 resection. The interval time between the last drug treatment and surgery was 3 to 5 weeks, with a median of 4 weeks. No surgical complications occurred. 1 patient achieved pCR (pathological complete response), and the MPR (major pathological response) rate was 41.67%. 11 patients (91.67%) achieved postoperative downstaging of T and/or N stage.Follow-up continued until December 2025, with a median follow-up duration of 18 months. 4 patients developed disease progression, including 3 local recurrence and 1 distant metastasis. One patient who did not achieve downstaging experienced local recurrence more than a month after surgery and died eight months post-operation;The 6-month DFS (disease-free survival) rate was 91.67%. The incidence of grade ≥3 adverse events (AE) was 58.33%, The most frequent grade≥3 AE was leukopenia，neutropenia and lymphocytes decreased. AEs led to a reduction in the dosage of chemotherapy drugs for one patient and a delay in the treatment time for one patient. There was no treatment discontinuation and deaths due to AEs. Conclusions: In this retrospective study, cetuximab combined with immunotherapy and chemotherapy can achieve a surgical downstaging effect without increasing surgical complications, and show encouraging efficacy and tolerability in the preoperative induction therapy of LA-HNSCC.