A randomized phase II trial of cetuximab-based induction chemotherapy followed by concurrent cetuximab, 5-FU, hydroxyurea, and hyperfractionated radiation (CetuxFHX), or cetuximab, cisplatin, and accelerated radiation with concomitant boost (CetuxPX) in patients with locoregionally advanced head and neck cancer (HNC).

Abstract

5519 Background: Cetuximab is commonly used in combination with either chemotherapy or radiation in the treatment of HNC, although the optimal way to integrate cetuximab with concurrent chemoradiation (CRT) remains unclear. We explored the addition of cetuximab to induction chemotherapy and two established CRT platforms in a randomized phase II trial. Methods: Patients with locoregionally advanced HNC were treated with cetuximab, carboplatin, paclitaxel induction chemotherapy for 2 cycles. Patients were randomized to A: cetuximab, 5-FU, hydroxyurea, and hyperfractionated week-on week-off RT (72-74Gy) (CetuxFHX), or B: cetuximab, cisplatin, accelerated radiation with concomitant boost (CetuxPX)(72Gy). Primary endpoints were 1- and 2-year progression-free (PFS), and overall survival (OS). Results: 110 patients with locoregionally advanced HNC (108 with Stage IV) were enrolled. 57.3% of patients had oropharyngeal (OP) primaries (A: 49%, B: 66%, p16 staining is pending). Induction response rate was 91.8%. 99.1% of patients developed a rash (≥grade 3 in 16.4%); ≥grade 3 neutropenia developed in 36.3% of patients. Overall 1- and 2-year survival rates were 98.3% and 89.5% in CetuxFHX, and 94.2% and 91.4% in CetuxPX arm, with 21.1months median follow-up (not statistically significant, p=0.27, logrank test). Progression free survival at 1 and 2 years was 86.0% and 82.3% in CetuxFHX, and 95.9% and 89.7% in CetuxPX (p=0.18). Grade ≥3 mucositis was present in 91.1%(A) and 94.3%(B) of patients; grade ≥3 dermatitis in 82.1% and 50.9% of patients. 95% of patients completed therapy. Treatment failures occurred in both OP and non-OP tumors. Conclusions: Cetuximab-based induction chemotherapy is well tolerated and active. Cetuximab can safely be integrated with both FHX and cisplatin based CRT with acceptable toxicities. Survival is favorable on both study arms suggesting that either platform could be investigated further. Data on HPV versus non-HPV-related tumors will be available.