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


REGISTERED CLINICAL TRIAL NUMBER
NCT00798655.
['Ferris|R L|RL|', 'Geiger|J L|JL|', 'Trivedi|S|S|', 'Schmitt|N C|NC|', 'Heron|D E|DE|', 'Johnson|J T|JT|', 'Kim|S|S|', 'Duvvuri|U|U|', 'Clump|D A|DA|', 'Bauman|J E|JE|', 'Ohr|J P|JP|', 'Gooding|W E|WE|', 'Argiris|A|A|']
D000328:Adult D000368:Aged D000911:Antibodies, Monoclonal D000971:Antineoplastic Combined Chemotherapy Protocols D002294:Carcinoma, Squamous Cell D002945:Cisplatin D003131:Combined Modality Therapy D018572:Disease-Free Survival D066246:ErbB Receptors D005260:Female D006258:Head and Neck Neoplasms D006801:Humans D008297:Male D008875:Middle Aged D009364:Neoplasm Recurrence, Local D009367:Neoplasm Staging D000077544:Panitumumab D000077195:Squamous Cell Carcinoma of Head and Neck
panitumumab head and neck squamous cell carcinoma cisplatin chemoradiotherapy clinical trial