Multicenter phase 3 trial of proton versus photon radiotherapy for patients with oropharyngeal cancer

A phase 3 trial at 21 centers in the USA compared intensity-modulated radiation therapy (IMRT) versus intensity-modulated proton therapy (IMPT), both concurrent with systemic therapy, for adult patients with stage III or IV oropharyngeal cancer and an ECOG performance status of 0-2. All patients were treated with radiotherapy to 70 Gy in 33 fractions to the primary tumor site and cervical lymphadenopathy. At a median follow-up time of 3.2 years, progression-free survival rates for the IMPT group were 82.5% at 3 years and 81.3% at 5 years; corresponding rates for the IMRT group were 83.0% and 76.2% (p=0.005 for noninferiority of IMPT). Overall survival rates at 5 years were 90.9% after IMPT versus 81.0% after IMRT (HR 0.58; p=0.045). Treatment-related deaths occurred in 3 of 160 patients in the IMPT group and 6 of 136 patients in the IMRT group. Severe lymphopenia, dysphagia, xerostomia, and gastrostomy tube dependence were more common in the IMRT group than in the IMPT group. The authors conclude that IMPT showed noninferiority to IMRT for progression-free survival, improvement in overall survival, and reduced high-grade toxicity.