A randomized phase III trial (RTOG 0522) of concurrent accelerated radiation plus cisplatin with or without cetuximab for stage III-IV head and neck squamous cell carcinomas (HNC).

5500 Background: The concurrent use of cisplatin (CDDP) or cetuximab (CET) with radiation (RT) has been shown to improve survival of patients with stage III-IV HNC. Since CET enhances the response of metastatic HNC to platinum-containing regimens and survival, the RTOG launched a phase III trial to test the hypothesis that adding CET to the RT-CDDP platform for frontline therapy of stage III-IV HNC improves progression free survival. Methods: Patients with stage III-IV carcinoma of the oropharynx, larynx, and hypopharynx, having Zubrod performance of 0-1, and meeting predefined blood chemistry criteria were enrolled after providing consent. The experimental regimen (Arm A) consisted of a loading dose and 6-7 weekly doses of CET given in conjunction with the control arm (B) of 70-72 Gy (6 weeks) + 2 cycles of CDDP (q3 weeks). Results: From 11/’05 to 3/’09, 940 patients were enrolled. Of the 895 evaluable patients, 447 randomized to Arm A and 448 to Arm B. Over 90% of patients received 2 CDDP cycles in both arms and 74% of cases received the loading plus 6 or more doses of CET in Arm A. The median follow-up was 2.4 years for surviving patients. There were no significant differences in progression-free survival (HR [A/B]: 1.05, 0.84-1.29; P=0.66; 2-Y rates: 63% vs. 64%), the primary endpoint, or in overall survival (HR: 0.87, 0.66-1.15; P=0.17; 2-Y rates: 83% vs. 80%), death within 30 days of therapy (2.0% vs. 1.8%, P=0.81), and total grade 3-5 adverse events (92% vs. 90%, P=0.30). Arm A had higher rates of grade 3-4 mucositis (45% vs. 35%, P=0.003) and skin reactions (40% vs. 17%, P<0.0001) but grade 3-4 dysphagia rates were not significantly different (62% vs. 66%, P=0.27). Conclusions: The addition of cetuximab to the radiation-cisplatin platform did not improve progression-free or overall survival. The triplet regimen was associated with higher rates of mucositis and CET-induced skin reactions but no unexpected toxicity was observed. Whether tumor human papillomavirus status would affect the relative efficacy of the triplet regimen and the overall outcome of this trial is being addressed. Funding: NCI U10CA21661, U10CA37422, and Bristol-Myers Squibb.