Dr Mehra on Transoral Surgery and Risk-Based Radiation in HPV+ Oropharynx Cancer

Ranee Mehra, MD, professor of medicine; director, Head and Neck Medical Oncology; head, Solid Tumor Section; and interim associate director, Clinical Research, University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center, discusses long-term results from the phase 2 E3311 trial (NCT01898494) exploring primary transoral surgery and postoperative radiation deintensification strategies for patients with human papillomavirus (HPV)–associated oropharynx cancer.

During the study, patients with HPV-associated oropharynx cancer underwent transoral resection with neck dissection, and postoperative treatment was based on risk. Patients with low-risk disease underwent observation (arm A); those with high-risk disease received intensity-modulated radiation therapy (IMRT) at 66 Gy in 33 fractions in combination with cisplatin (arm D). Notably, patients with intermediate-risk disease were randomly assigned to receive IMRT at 50 Gy in 25 fractions (arm B) or 60 Gy in 30 fractions (arm C).

Findings presented at the 2024 ASCO Annual Meeting showed that at a median follow-up of 52.4 months, progression-free survival (PFS) and overall survival (OS) data remained favorable across all treatment groups, Mehra explains. The 54-month PFS rates were 93.2% for arm A, 94.9% for arm B, 90.2% for arm C, and 85.5% for arm D. The respective 54-month OS rates were 97.1%, 97.9%, 95.1%, and 92.5%.

Notably, smoking history did not influence outcomes across treatment cohorts, Mehra says. However, in arm A, 14.8% of patients with N1 disease (n = 27) experienced recurrence, whereas no patients with N0 disease in this arm (n = 11) had disease recurrence. Mehra explains that the recurrence observed in patients with low-risk, N1 disease warrant further exploration.

Mehra adds that in arm D, patients with high-risk oropharynx cancer—defined as either extra nodal-extension or positive surgical margins—experienced favorable outcomes relative to historical controls when treated with radiation and cisplatin. However, despite intensified therapy, patients in this arm had numerically lower 5-year OS and PFS rates compared with other groups, suggesting the need for more aggressive treatment approaches for those with higher-risk disease.