Abstract IA20: Radiotherapy plus cetuximab or cisplatin in human papilloma-virus positive oropharyngeal cancer (NRG 1016): A randomized multicenter noninferiority trial*
Authors: Ridge J.A. , Ringash J. , Yao M. , Blakaj D.M. , Razaq M.A. , Colevas A.D. , Beitler J.J. , Jones C.U. , Dunlap N.E. , Seaward S.A. , Spencer S. , Galloway T.J. , Dignam J.J. , Le Q.T. , Gillison M.L. , Sturgis E.M. , Phan J. , Trotti A.M. , Harris J. , Eisbruch A. , Harari P.M. , Adelstein D.J. , Koyfman S.A. , Burtness B. 
Published: September 2020

Abstract
Background: Patients with HPV-related oropharynx cancer have high survival when treated with radiotherapy plus cisplatin. Whether replacement of cisplatin with cetuximab can preserve high survival and reduce toxicity is unknown. We performed a randomized trial comparing survival and toxicity in 987 patients enrolled at 182 health care centers in the US and Canada between July 2011 and July 2014.
Methods: Eligibility included histologically confirmed HPV positive carcinoma, clinical stage TI-T2, N2-N3 or T3-T4, N0-N3. Zubrod status 0 or 1. All patients received intensity modulated radiotherapy (IMRT) delivered in 35 fractions to 70 gray over 6 weeks using 6 fractions per week. High-dose cisplatin at 100 mg/m² was given every 3 weeks for 2 cycles in arm A (standard of care) versus arm B loading dose cetuximab plus weekly cetuximab. Patients were stratified by T category, N category, Zubord performance status, and smoking history.
Primary analysis was based on modified intention to treat for all patients meeting eligibility criteria. 849 patients were randomly assigned to radiation plus cetuximab (425) or radiotherapy plus cisplatin (424). Median follow-up is 4.5 years.
Results: Radiotherapy plus cetuximab did not meet the non-inferiority criteria for overall survival. Estimated 5-year overall survival was 78% in the cetuximab group versus 85% in the cisplatin group (p=0.016). Progression-free survival was 67% versus 78% (p=0.0002). Local-regional failure was higher in the cetuximab group, 17% versus 10% (p=0.005). High-grade acute toxicity was similar at 77% for both groups. Late toxicity was also similar.
Conclusions: For HPV-positive oropharyngeal carcinoma, radiotherapy plus cetuximab showed inferior overall survival, progression-free survival, and locoregional control compared with radiation plus cisplatin. This study defines radiation using IMRT plus cisplatin as the standard of care for this population.
*Lancet. Vol 393, p 40-50, January 5, 2019
Citation Format: J.A. Ridge, J. Ringash, M. Yao, D.M. Blakaj, M.A. Razaq, A.D. Colevas, J.J. Beitler, C.U. Jones, N.E. Dunlap, S.A. Seaward, S. Spencer, T.J. Galloway, J.J. Dignam, Q.T. Le, M.L. Gillison, E.M. Sturgis, J. Phan, A.M. Trotti, J. Harris, A. Eisbruch, P.M. Harari, D.J. Adelstein, S.A. Koyfman, B. Burtness. Radiotherapy plus cetuximab or cisplatin in human papilloma-virus positive oropharyngeal cancer (NRG 1016): A randomized multicenter noninferiority trial [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Optimizing Survival and Quality of Life through Basic, Clinical, and Translational Research; 2019 Apr 29-30; Austin, TX. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(12_Suppl_2):Abstract nr IA20.