2766 - Initial Results of a Prospective Study of Quad-Shot Radiotherapy in Combination with Immune Checkpoint Inhibition for Advanced/Recurrent Head and Neck Cancer
Presenter(s)
R. T. Hughes1, B. A. Frizzell1, S. Smith2, R. D'Agostino Jr3, P. M. Bunch4, T. Lycan5, P. Triozzi6, C. M. Furdui7, and M. Porosnicu6; 1Department of Radiation Oncology, Wake Forest University School of Medicine, Winston Salem, NC, 2Department of Biostatistics and Data Science, Wake Forest University School of Medicine, Winston Salem, NC, 3Department of Biostatistics and Data Science, Wake Forest University School of Medicine, Winston -Salem, NC, 4Department of Radiology, Wake Forest University School of Medicine, Winston Salem, NC, 5Department of Internal Medicine, Section of Hematology and Oncology, Wake Forest University School of Medicine, Winston-Salem, NC, 6Department of Internal Medicine, Section of Hematology and Oncology, Wake Forest University School of Medicine, Winston Salem, NC, 7Department of Internal Medicine, Section of Molecular Medicine, Wake Forest University School of Medicine, Winston Salem, NC
Purpose/Objective(s): For patients with incurable, advanced/recurrent head and neck squamous cell carcinoma (A/R HNSCC) treated with immune checkpoint inhibition (ICI) alone, response and disease control rates are modest. The delivery of quad-shot radiotherapy (QS RT) to locoregional disease may improve response rates and the durability of response. We aimed to assess rates of response and survival in patients with A/R HNSCC treated with QS RT delivered in combination with ICI.
Materials/Methods: In this single-arm prospective study, patients with A/R HNSCC were enrolled and treated with pembrolizumab 200 mg/m2 every 3 weeks. QS RT comprised 14.8 Gy delivered to the gross disease in the head and neck in 4 twice-daily fractions over 2 days; at least 1 and up to 3 courses of QS RT were delivered at investigators’ discretion between cycles 2-4, 6-8, and 11-13, optimally within 1 week of upcoming dose. Patients who received at least 3 cycles of ICI and at least 1 QS RT were deemed eligible for analysis; those who did not (for any reason) were replaced. The primary endpoint was overall response rate (ORR, defined as partial or complete response) determined by RECIST 1.1 every 5 cycles; secondary outcomes were progression-free survival (PFS), overall survival (OS), toxicity at least possibly related to treatment per CTCAE v5.0, and HSNCC-specific quality of life (QOL) measured by the patient-reported outcome CTCAE (PRO-CTCAE) v1.0. For this initial report of early outcomes, data cutoff occurred on 12/11/2024.
Results: In total, patients were enrolled, and 15 were eligible for analysis. Median age was 61; 10 patients were male, 10 had T3-4 disease, 7 had N2-3 disease, 14 were current/former smokers, 8 had at least 1 line of prior systemic therapy for A/R HNSCC, and 3 had known PDL1 CPS score (range: 0-30). The median number of prior RT courses was 1 (range: 0-2) with a median prior exposure of 63 Gy (range: 0-119). 8/5/2 patients had a total of 1/2/3 QS RT during ICI. The ORR was 43% (95% CI 18-71) after 5 cycles of ICI (n=14 evaluable) and 56% (95% CI 21-86) after 10 cycles (n=9). Median follow-up for eligible patients was 10 months (range, 5-30). Median PFS was 11.5 months; median OS was 23.7 months. Rates of CTCAE grade 3 or 4 adverse events were 33% (95% CI 12-62) and 13% (95% CI 2-41). Most patients reported worsening of at least one PRO-CTCAE measure (e.g., pain, fatigue, xerostomia, dysphagia) by at least 1 point (n=15) and 2 points (n=14). The mean change from baseline for all items was <1.
Conclusion: In this prospective trial of QS RT combined with ICI for patients with A/R HNSCC, we found this novel combination to be feasible, tolerable and associated with favorable response and survival rates. Additional prospective study of this regimen is warranted.