Methotrexate plus or minus cetuximab as first‐line treatment in a recurrent or metastatic (R/M) squamous cell carcinoma population of the head and neck (SCCHN), unfit for cisplatin combination treatment, a phase Ib‐randomized phase II study Commence

Background Methotrexate in recurrent or metastatic (R/M) squamous cell carcinoma of the head and neck (SCCHN) has limited progression‐free survival (PFS) benefit. We hypothesized that adding cetuximab to methotrexate improves PFS. Methods In the phase‐Ib‐study, patients with R/M SCCHN received methotrexate and cetuximab as first‐line treatment. The primary objective was feasibility. In the phase‐II‐study patients were randomized to this combination or methotrexate alone (2:1). The primary endpoint was PFS. Secondary endpoints were overall survival (OS), toxicity, and quality of life (QoL). Results In six patients in the phase‐Ib‐study, no dose limiting toxicities were observed. In the phase II study, 30 patients received the combination and 15 patients methotrexate. In the phase‐II‐study median PFS was 4.5 months in the combination group vs 2.0 months in the methotrexate group (HR 0.37; P = .002). OS, toxicity, and QoL were not significantly different. Conclusion Cetuximab with methotrexate improved PFS without increased toxicity in R/M SCCHN‐patients.