The final results of the randomized phase II ECOG-ACRIN E3311 trial were presented by Robert L. Ferris, MD, PhD, and colleagues during the ASCO20 Virtual Scientific Program (Abstract 6500) and in today's Head and Neck Cancer Oral Abstract Session. The trial, conducted in patients undergoing transoral robotic surgery, tested reduced postoperative radiation therapy in patients with human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma at intermediate risk for recurrence.
“Transoral resection followed by low-dose radiation is safe in patients with intermediate-risk locally advanced oropharyn[geal] cancer, with very good oncologic outcome."— Robert L. Ferris, MD, PhD
Tweet this quote
“Transoral resection followed by low-dose radiation is safe in patients with intermediate-risk locally advanced oropharyn[geal] cancer, with very good oncologic outcome,” said lead investigator Dr. Ferris, Director of the University of Pittsburgh Medical Center Hillman Cancer Center and a surgical oncologist specializing in head and neck cancer. “These results present a promising deintensification approach.”
Study Background and Details
Most patients with oropharyngeal cancers caused by HPV have a very good outcome, and the cancer does not return or spread to other parts of the body after treatment. Dr. Ferris and colleagues sought to prove the benefits of using tumor pathologic features, obtained in specimens collected at surgery, to determine patients’ risk of recurrence-low, -intermediate or -high disease. In particular, they sought to more clearly define the prognostic and predictive role of traditional pathologic biomarkers—such as extensive nodal or extranodal disease—to give the right amount of postoperative treatment for each risk group.
Patients at low risk of recurrence were observed. Patients at intermediate risk were randomly assigned to two arms of radiation alone, both at doses lower (50 or 60 Gy) than usual (60 to 66 Gy). At the time the trial opened in 2013, the optimal dose of radiation therapy was not defined. Patients at high risk were assigned to usual radiation therapy plus chemotherapy.
The primary endpoint was 2-year progression-free survival in patients determined to be at intermediate risk after surgical excision.
Findings
“Study E3311 met its primary endpoint,” said Dr. Ferris. “For intermediate-risk patients—those with uninvolved surgical margins, less than five involved nodes, and less than 1 mm extranodal extension—reduced-dose postoperative radiation therapy without chemotherapy appears sufficient. In our study, this group had better outcomes than the group on usual high-dose radiation plus chemotherapy, showing that our patient stratification identified low- and intermediate-risk patients well, preserving patients’ throat function and sparing them unnecessary short- and long-term toxicities.”
For patients with low-risk disease, 2-year progression-free survival was favorable without postoperative therapy (observation alone). All arms had 2-year survival rates above 90%, and there was no excess of local recurrences with reduction in radiation or chemotherapy (arms B and C). Risk stratification appeared to appropriately select patients for observation (arm A).
The study authors concluded, “Transoral resection of p16-positive [oropharyngeal cancer] is safe and results in good oncologic outcome, presenting a promising deintensification approach. For patients with low-risk disease, 2-year progression-free survival is favorable without postoperative therapy. For those with uninvolved surgical margins, fewer than five involved nodes, and minimal extranodal extension, reduced-dose postoperative radiotherapy without chemotherapy appears sufficient. Transoral surgery plus 50 Gy should be compared to optimal nonsurgical therapy in a phase III trial.”
Next Steps
The overall intent of E3311 was to gather essential data for the design of a future randomized phase III trial. The primary endpoint was to determine the feasibility and oncologic efficacy of a prospective multi-institutional study of transoral robotic surgery for HPV-associated oropharyngeal cancer followed by risk-adjusted adjuvant therapy.
Barbara A. Burtness, MD
“The tissue samples and imaging studies collected in the course of this trial are a rich resource for studying the biology of intermediate- and high-risk disease, in work that is ongoing,” said ECOG-ACRIN Head and Neck Committee Chair Barbara A. Burtness, MD, Professor of Medicine and Co-Leader, Developmental Therapeutics Program, Yale Cancer Center and Yale School of Medicine. “ECOG-ACRIN plans to pursue the current data with a randomized phase III trial of transoral robotic surgery–based treatment deintensification compared with conventional chemoradiation.”
Disclosure: For full disclosures of the study authors, visit coi.asco.org.
