3427 - Perioperative Pembrolizumab and Intraoperative Radiation with or without Preoperative Radiotherapy in Recurrent/Persistent Head and Neck Squamous Cell Carcinoma: Interim Analysis of a Randomized Pilot Trial
Presenter(s)
S. Baliga1, M. Bonomi2, M. Old3, J. Pan4, E. Gogineni5, D. L. Mitchell5, D. J. Konieczkowski5, N. Seim6, C. T. Haring6, K. VanKoevering7, A. Agrawal6, E. Ozer8, N. Mladkova9, L. Miller6, E. M. Tili10, P. Bhateja2, J. W. Rocco6, A. Chakravarti5, J. C. Grecula5, and D. M. Blakaj5; 1Department of Radiation Oncology, James Cancer Hospital, The Ohio State University Medical Center, Columbus, OH, 2The Ohio State University Wexner Medical Center, Columbus, OH, 3University of Washington, Seattle, WA, 4The Ohio State University Wexner Medical Center, Center for Biostatistics, Columbus, OH, 5Department of Radiation Oncology, James Cancer Hospital/Wexner Medical Center, The Ohio State University, Columbus, OH, 6The Ohio State University Department of Otolaryngology - Head & Neck Surgery, Columbus, OH, 7The Ohio State University, Columbus, OH, 8Ohio State University Comprehensive Cancer Center, Columbus, OH, 9Westchester Medical Center, New York Medical College, Valhalla, NY, 10Ohio State University, Columbus, OH
Purpose/Objective(s): Patients with loco-regionally recurrent or persistent head and neck squamous cell carcinoma (rHNSCC) have a poor prognosis, with low rates of loco-regional control (LRC) and overall survival(OS) after salvage surgery alone. The use of preoperative external beam radiation therapy (EBRT) with immunotherapy and intraoperative radiation therapy (IORT), in addition to surgery, may improve clinical efficacy without increasing toxicity. We conducted a randomized pilot study to evaluate the safety and efficacy of perioperative pembrolizumab combined with intraoperative radiation therapy (IORT), with or without preoperative external beam radiation therapy (EBRT), in resectable recurrent or persistent HNSCC.
Materials/Methods: This is a single institution, randomized three arm pilot study enrolling 45 patients with resectable persistent or loco-regionally recurrent HNSCC of the oral cavity, pharynx, and/or larynx. Patients were randomized 1:1:1 to perioperative pembrolizumab with IORT alone or with the addition of preoperative EBRT delivered as either 2 Gy × 2 or 8 Gy × 2 prior to surgery. All patients received 1-2 preoperative doses of pembrolizumab (200 mg/dose) followed by salvage surgery with IORT (10–15 Gy) and up to 18 postoperative doses of pembrolizumab. The primary endpoint was treatment-related grade 3–4 toxicity (CTCAE v4.0). Pre-specified stopping criteria included, within the first 15 patients, any Grade 5, >13% Grade 4, or >25% Grade 3 toxicity attributable to RT. Overall Survival (OS), progression free survival (PFS), and loco-regional control (LRC) were estimated using the Kaplan Meier analysis method. Herein, we report the interim analysis of the first 15 patients.
Results: As of December 2025, 15 patients were enrolled (5 per arm). Disease location included oral cavity (n=8), oropharynx (n=3), larynx (n=2), and parotid (n=2). Median follow-up was 14.9 months, and median age was 68 years. The median IORT dose was 15 Gy delivered to the 90% isodose line. A total of 35 grade 3–4 adverse events were observed (33 grade 3; 2 grade 4). Only 3 events in two patients (all grade 3) were attributed to radiotherapy. Three patients died (20%), of which two were due to local recurrence and one due to aspiration pneumonia. There were no distant failures. The 1-year OS, PFS and LRC was 80% (95% CI: 50%-93%), 73% (95% CI:44%-89%), and 85% (95% CI:52%-96%).
Conclusion: Perioperative pembrolizumab combined with IORT, with or without preoperative EBRT, appears feasible and did not trigger protocol-defined stopping criteria in this interim analysis. Local control was excellent compared to historical controls. High grade toxicity attributable to radiotherapy was uncommon. Continued accrual and longer follow-up are required to further define safety and assess potential efficacy signals.