Cetuximab plus Postoperative Radiotherapy for Intermediate Risk Head and Neck Cancer?

Postoperative chemoradiation with cisplatin is the standard of care for locally advanced head and neck squamous cell carcinoma (HNSCC) in patients with high risk for recurrence (e.g., pathologic findings of positive margins, extranodal extension of tumor). Whether patients with intermediate-risk disease would benefit from concurrent systemic therapy with postoperative radiation is unclear.

This multicenter, open-label, randomized phase 3 trial evaluated the efficacy of adding cetuximab to postoperative radiotherapy (RT) in patients with resected intermediate-risk HNSCC (close [<5 mm] resection margins, pathologic stage T3 or T4a tumors, pathologic N2 disease, lymphovascular or perineural invasion, or T2 oral cavity cancer with >5mm depth of invasion).

Of 577 patients randomized to RT alone or RT plus cetuximab, 18% had HPV-positive oropharynx cancer, and the majority had HPV-negative oral cavity (63.6%) or larynx (14.2%) cancers. At a median follow-up of 7.2 years, the addition of cetuximab to postoperative RT did not significantly improve overall survival (the primary endpoint) compared with RT alone (hazard ratio, 0.81; P=0.08) but did significantly improve disease-free survival (HR, 0.75; P=0.02). Cetuximab was associated with more grade 3–4 adverse events than RT alone (70.3% vs. 39.7%), particularly lymphopenia and dermatologic and infusion-related events.