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

Background Immunotherapy has 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 immune checkpoint inhibitors. This study evaluated the real-world efficacy and safety of combining immunotherapy with anti-EGFR agents in patients with R/M HNSCC. Methods 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 immunotherapy 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. Results A total of 29 patients were included in the analysis. The cohort was characterized by a high proportion of platinum-refractory disease (59%) and 38% of patients received the combination as second-line treatment or later. The ORR was 44% (95% CI: 26%–64%), including 3 complete responses (10%) and 10 partial responses (34%). The DCR was 66%. The median PFS was 6.9 months (95% CI: 2.9–9.2), and the median OS was 15.1 months (95% CI: 8.4–not reached). Notably, in the subgroup with a PD-L1 combined positive score (CPS) < 1, the ORR was 37.5%. Treatment-related adverse events occurred in 79% of patients but were exclusively Grade 1 or 2; no Grade 3 or higher adverse events were observed. Conclusion The combination of immunotherapy and anti-EGFR agents demonstrated promising antitumor activity and a favorable safety profile in patients with R/M HNSCC. These findings suggest this regimen may be a viable therapeutic strategy, particularly for patients with platinum-refractory disease or low PD-L1 expression who traditionally have poor outcomes.