Phase II trial of post-operative radiotherapy with concurrent cisplatin plus panitumumab in patients with high-risk, resected head and neck cancer

Addition of panitumumab to adjuvant chemoradiation is tolerable and provides promising clinical acivity for high risk, resected head and neck squamous cell carcinoma. Background: Treatment intensification for resected, high-risk, head and neck squamous cell carcinoma (HNSCC) is an area of active investigation with novel adjuvant regimens under study. In this trial, the epidermal growth-factor receptor (EGFR) pathway was targeted using the IgG2 monoclonal antibody panitumumab in combination with cisplatin chemoradiotherapy (CRT) in high-risk, resected HNSCC. Patients and methods: Eligible patients included resected pathologic stage III or IVA squamous cell carcinoma of the oral cavity, larynx, hypopharynx, or human-papillomavirus (HPV)-negative oropharynx, without gross residual tumor, featuring high-risk factors (margins <1 mm, extracapsular extension, perineural or angiolymphatic invasion, or ≥2 positive lymph nodes). Postoperative treatment consisted of standard RT (60–66 Gy over 6–7 weeks) concurrent with weekly cisplatin 30 mg/m² and weekly panitumumab 2.5 mg/kg. The primary endpoint was progression-free survival (PFS). Results: Forty-six patients were accrued; 44 were evaluable and were analyzed. The median follow-up for patients without recurrence was 49 months (range 12–90 months). The probability of 2-year PFS was 70% (95% CI = 58%–85%), and the probability of 2-year OS was 72% (95% CI = 60%–87%). Fourteen patients developed recurrent disease, and 13 (30%) of them died. An additional five patients died from causes other than HNSCC. Severe (grade 3 or higher) toxicities occurred in 14 patients (32%). Conclusions: Intensification of adjuvant treatment adding panitumumab to cisplatin CRT is tolerable and demonstrates improved clinical outcome for high-risk, resected, HPV-negative HNSCC patients. Further targeted monoclonal antibody combinations are warranted.