The Administration of Cetuximab-Based Regimen as a Second Line After Pembrolizumab Among Incurable Head and Neck Squamous Cell Carcinoma Patients

In the last years, combination of Pembrolizumab and chemotherapy has become standard of care first-line treatment among advanced-stage or metastatic head and neck squamous cell carcinoma (HNSCC) patients. However, the response rate for this treatment is still low, and most patients eventually progress, creating an unmet need for a standard second-line treatment. We aim to describe our experience with HNSCC patients who progress on Pembrolizumab and are treated with Cetuximab with or without chemotherapy. We performed a retrospective review of HNSCC patients who experienced disease progression after Pembrolizumab therapy (with or without chemotherapy) and subsequently received Cetuximab-containing regimens as second-line treatment, at a university-affiliated tertiary care center between 2019 and 2023. The study cohort comprised 21 patients whose disease progressed after a Pembrolizumab-containing first-line regimen. (mean age at HNSCC diagnosis: 66.3±13.2 y). Primary sites of origin were predominantly the oral cavity (52.4%, n=11) and oropharynx (19%, n=4). Treatment outcomes were as follows: complete response (14.3%, n=3), partial response (38.1%, n=8), stable disease (19.1%, n=4), and progression of disease (28.6%, n=6). The overall response rate was 52.4%, with a disease control rate of 71.4%. Median progression-free survival was 7.3 months (range: 1-38.3 mo). Cetuximab-containing second-line regimens demonstrated promising efficacy in HNSCC patients who progressed on Pembrolizumab-based protocols, yielding favorable response rates and durable responses. These findings warrant further investigation through prospective clinical trials to establish consensus guidelines for this patient population.