1. Radiotherapy plus cetuximab or cisplatin in human papillomavirus-positive oropharyngeal cancer (NRG Oncology RTOG 1016): a randomised, multicentre, non-inferiority trial.
- Author
-
Gillison, Maura L, Gillison, Maura L, Trotti, Andy M, Harris, Jonathan, Eisbruch, Avraham, Harari, Paul M, Adelstein, David J, Jordan, Richard CK, Zhao, Weiqiang, Sturgis, Erich M, Burtness, Barbara, Ridge, John A, Ringash, Jolie, Galvin, James, Yao, Min, Koyfman, Shlomo A, Blakaj, Dukagjin M, Razaq, Mohammed A, Colevas, A Dimitrios, Beitler, Jonathan J, Jones, Christopher U, Dunlap, Neal E, Seaward, Samantha A, Spencer, Sharon, Galloway, Thomas J, Phan, Jack, Dignam, James J, Le, Quynh Thu, Gillison, Maura L, Gillison, Maura L, Trotti, Andy M, Harris, Jonathan, Eisbruch, Avraham, Harari, Paul M, Adelstein, David J, Jordan, Richard CK, Zhao, Weiqiang, Sturgis, Erich M, Burtness, Barbara, Ridge, John A, Ringash, Jolie, Galvin, James, Yao, Min, Koyfman, Shlomo A, Blakaj, Dukagjin M, Razaq, Mohammed A, Colevas, A Dimitrios, Beitler, Jonathan J, Jones, Christopher U, Dunlap, Neal E, Seaward, Samantha A, Spencer, Sharon, Galloway, Thomas J, Phan, Jack, Dignam, James J, and Le, Quynh Thu
- Abstract
BackgroundPatients with human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma have high survival when treated with radiotherapy plus cisplatin. Whether replacement of cisplatin with cetuximab-an antibody against the epidermal growth factor receptor-can preserve high survival and reduce treatment toxicity is unknown. We investigated whether cetuximab would maintain a high proportion of patient survival and reduce acute and late toxicity.MethodsRTOG 1016 was a randomised, multicentre, non-inferiority trial at 182 health-care centres in the USA and Canada. Eligibility criteria included histologically confirmed HPV-positive oropharyngeal carcinoma; American Joint Committee on Cancer 7th edition clinical categories T1-T2, N2a-N3 M0 or T3-T4, N0-N3 M0; Zubrod performance status 0 or 1; age at least 18 years; and adequate bone marrow, hepatic, and renal function. We randomly assigned patients (1:1) to receive either radiotherapy plus cetuximab or radiotherapy plus cisplatin. Randomisation was balanced by using randomly permuted blocks, and patients were stratified by T category (T1-T2 vs T3-T4), N category (N0-N2a vs N2b-N3), Zubrod performance status (0 vs 1), and tobacco smoking history (≤10 pack-years vs >10 pack-years). Patients were assigned to receive either intravenous cetuximab at a loading dose of 400 mg/m2 5-7 days before radiotherapy initiation, followed by cetuximab 250 mg/m2 weekly for seven doses (total 2150 mg/m2), or cisplatin 100 mg/m2 on days 1 and 22 of radiotherapy (total 200 mg/m2). All patients received accelerated intensity-modulated radiotherapy delivered at 70 Gy in 35 fractions over 6 weeks at six fractions per week (with two fractions given on one day, at least 6 h apart). The primary endpoint was overall survival, defined as time from randomisation to death from any cause, with non-inferiority margin 1·45. Primary analysis was based on the modified intention-to-treat approach, whereby all patients meeting eligibility crite
- Published
- 2019