The Phase I/II ACCEPT Trial: Concurrent Cetuximab and Intensity-Modulated Radiotherapy with Carbon Ion Boost for Adenoid Cystic Carcinoma of the Head and Neck: Cetuximab and IMRT/Carbon Ions for ACC

Abstract Introduction The adenoid cystic carcinoma ( ACC), Erbitux®, and Particle Therapy (xxx) phase I/II trial (NCTxxx) evaluated a combined-modality approach (concurrent cetuximab and intensity-modulated radiotherapy (IMRT) with carbon ion (CIRT) boost) for newly-diagnosed nonmetastatic head and neck ACC. Methods Twenty-three patients with ACC were enrolled between June 2012 and June 2017 following initial diagnosis or postoperatively. All received a 400 mg/m2 cetuximab loading dose a week before radiotherapy, followed by weekly 250 mg/m2 doses starting on the first day of radiotherapy. The CIRT boost was 24 Gy(RBE) in 8 daily fractions, followed by IMRT (54 Gy). The primary endpoint was safety and feasibility (defined based on CTCAE grade ≥3 events). Secondary endpoints included local and distant relapses, disease-free survival (DFS), and overall survival (OS). Results Disease was most commonly in the paranasal sinuses (30%), palate (17%), and nasopharynx (17%). Nine (39%) patients underwent surgery (R1: 22%, R2: 78%). Median follow-up was 38.5 months. No patients experienced grade 4-5 events. Rates of grade 3 rash and radiation dermatitis were 17% and 22%, respectively. Grades 2 and 3 mucositis and dysgeusia occurred in 43% & 48% and 9% & 0%, respectively. Grades 2-3 dysphagia and xerostomia were present in 43% & 4% and 26% & 0%, respectively. At last follow-up, 5 (22%) patients experienced in-field relapse and 6 (26%) developed distant metastases. The three-year DFS was 67%, and median OS was 54 months. Conclusions Outcomes of this trial were satisfactory. Although the trial did not meet the pre-defined criteria of feasibility, owing to the comparatively high rates of grade 3 dermatitis, the latter are numerically comparable to existing cetuximab+RT data.