As reported in JAMA Oncology by David Palma, MD, PhD, and colleagues, enrollment in the phase II ORATOR2 trial, which was designed to evaluate overall survival after de-escalated treatment with primary radiotherapy vs transoral surgery in human papillomavirus (HPV)-related oropharyngeal squamous cell carcinomas, was stopped early due to excess mortality in the transoral surgery group.
Study Details
The open-label trial included 61 patients with T1–2 N0–2 p16-positive oropharyngeal squamous cell carcinoma from sites in Canada and Australia. They were randomly assigned between February 2018 and November 2020 to primary radiotherapy consisting of 60 Gy with concurrent weekly cisplatin in node-positive patients (n = 30) or transoral surgery and neck dissection, with adjuvant reduced-dose radiotherapy, depending on pathologic findings (n = 31). The primary endpoint was overall survival compared with a historical control.
David Palma, MD, PhD
Key Findings
The trial began in February 2018, and accrual was halted in November 2020 due to excessive mortality in the transoral surgery and neck dissection group. Median follow-up was 17 months (interquartile range = 15–20 months).
Overall survival and progression-free survival data remained immature. A total of three deaths occurred, all in the transoral surgery and neck dissection group, including two treatment-related deaths due to oropharyngeal hemorrhage and cervical vertebral osteomyelitis (0.7 and 4.3 months after random assignment) and one due to myocardial infarction. A total of four progression-free survival events occurred, all in the transoral surgery and neck dissection group, including the three deaths and one local recurrence.
Grade ≥ 2 toxicity occurred in 67% of patients in the radiotherapy group and 71% of those in the transoral surgery and neck dissection group. Mean (SD) MD Anderson Dysphagia Inventory scores at 1 year were similar in the radiotherapy group and transoral surgery and neck dissection group (85.7 [15.6] vs 84.7 [14.5]).
The investigators concluded, “In this randomized clinical trial, transoral surgery was associated with an unacceptable risk of grade 5 toxic effects, but patients in both trial arms achieved good swallowing outcomes at 1 year. Long-term follow-up is required to assess overall survival and progression-free survival outcomes.”
Dr. Palma, of Western University, London, Ontario, Canada, is the corresponding author for the JAMA Oncology article.
Disclosure: The study was funded by an Ontario Institute for Cancer Research Grant and others. For full disclosures of the study authors, visit jamanetwork.com.
