Phase II Study of Cetuximab in Combination with Cisplatin and Radiation in Unresectable, Locally Advanced Head and Neck Squamous Cell Carcinoma: Eastern Cooperative Oncology Group Trial E3303
Mené sur 69 patients atteints d'un carcinome épidermoïde de la tête et du cou de stade IV et non résécable, cet essai de phase II évalue, du point de vue de la survie sans progression et de la survie globale à 2 ans, l'intérêt d'ajouter le cétuximab et le cisplatine à une radiothérapie
PURPOSE : Cisplatin or cetuximab combined with radiotherapy (RT) each yield superior survival in locally advanced squamous cell head and neck cancer (LA-SCCHN) compared to RT alone. E3303 evaluated the triple combination. EXPERIMENTAL DESIGN : Patients with stage IV unresectable LA-SCCHN received a loading dose of cetuximab (400mg/m2) followed by 250mg/m2/week and cisplatin 75mg/m2 q 3 weeks x3 cycles concurrent with standard fractionated RT. In the absence of disease progression or unacceptable toxicity, patients continued maintenance cetuximab for 6-12 months. Primary endpoint was 2-year progression-free survival (PFS). Patient tumor and blood correlates, including tumor human papillomavirus (HPV) status, were evaluated for association with survival. RESULTS : Sixty-nine patients were enrolled; 60 proved eligible and received protocol treatment. Oropharyngeal (OP) primaries constituted the majority (66.7%), stage T4 48.3% and N2-3 91.7%. Median RT dose delivered was 70 Gy, 71.6% received all 3 cycles of cisplatin and 74.6% received maintenance cetuximab. Median PFS was 19.4 months, 2-year PFS 47% (95%CI: 33-61%). 2-year overall survival (OS) was 66% (95%CI: 53-77%); median OS was not reached. Response rate was 66.7%. Most common grade >3 toxicities included mucositis (55%), dysphagia (46%) and neutropenia (26%); one attributable grade 5 toxicity occurred. Only tumor HPV status was significantly associated with survival. HPV was evaluable in 29 tumors; 10 (all OP) were HPV+. HPV+ patients had significantly longer OS and PFS (p=0.004 and p=0.036, respectively). CONCLUSIONS : Concurrent cetuximab, cisplatin and RT were well-tolerated and yielded promising 2-year PFS and OS in LA-SCCHN with improved survival for patients with HPV+ tumors.