Combination of immune checkpoint inhibitors and anti-EGFR agents in recurrent or metastatic head and neck squamous cell carcinoma: a single-center real-world cohort study

Immune checkpoint inhibitors (ICIs) have become a standard treatment for recurrent and/or metastatic head and neck squamous cell carcinoma (R/M HNSCC); however, response rates remain modest, and long-term survival is limited. Preclinical studies suggest that inhibiting the epidermal growth factor receptor (EGFR) pathway may enhance antigen presentation and augment the efficacy of ICIs. This study evaluated the real-world efficacy and safety of combining ICIs with anti-EGFR agents in patients with R/M HNSCC. We conducted a retrospective study at Taipei Veterans General Hospital involving patients diagnosed with R/M HNSCC between January 2020 and July 2024 who received combination therapy comprising ICIs and anti-EGFR agents. The primary endpoint was the objective response rate (ORR) according to RECIST v1.1. Secondary endpoints included disease control rate (DCR), progression-free survival (PFS), overall survival (OS), duration of response (DoR), and safety assessed by CTCAE v5.0. A total of 29 patients were evaluable for response (response-evaluable population), drawn from 38 combination-treated patients. The cohort was characterized by a high proportion of platinum-refractory disease (62%), and 34% of patients received the combination as second-line treatment or later. The ORR was 44.8% (95% CI 28.4–62.5%), including 3 complete responses (10.3%) and 10 partial responses (34.5%). The DCR was 65.5%. The median PFS was 7.4 months (95% CI 3.1–9.8), and the median OS was 16.8 months (95% CI 8.6–not reached), with a median follow-up of 17.6 months. In the subgroup with a PD-L1 combined positive score (CPS) < 1, the ORR was 37.5%. In a worst-case all-treated population sensitivity analysis including all 38 patients, the ORR was 34.2% and the median OS was 12.7 months. Treatment-related adverse events occurred in 83% of patients but were exclusively grade 1 or 2; no grade 3 or higher adverse events were observed. The combination of ICIs and anti-EGFR agents showed clinical activity that warrants further prospective investigation in patients with R/M HNSCC, including those with platinum-refractory disease or low PD-L1 expression who traditionally have poor outcomes. Given the retrospective, single-center design and the small sample size, these findings should be regarded as hypothesis-generating.