Real-world efficacy and safety of photoimmunotherapy for recurrent nasopharyngeal carcinoma: A nationwide multicenter study in Japan.

6030 Background: Treatment options for locally recurrent or residual nasopharyngeal carcinoma (NPC) after definitive radiotherapy remain limited. Salvage surgery is often challenging due to anatomical constraints, while re-irradiation and systemic therapies provide modest efficacy with substantial toxicity. Photoimmunotherapy (PIT) is a light-activated anticancer treatment targeting epidermal growth factor receptor (EGFR) that has been approved in Japan since September 2020 for unresectable locally advanced or locally recurrent head and neck cancers. However, real-world clinical data on PIT for recurrent NPC are limited. We conducted the NPC-PIT Study, a nationwide observational study evaluating the real-world efficacy and safety of PIT in patients with recurrent NPC. Methods: Patients with recurrent or residual NPC treated with PIT were enrolled from 26 institutions. Patients with at least 3 months of follow-up after initial PIT were evaluated. Clinical characteristics, prior treatments, PIT illumination techniques, treatment response, overall survival, EBV-DNA levels, and treatment-related adverse events were analyzed. Results: As of November 2025, 46 patients were enrolled. The four cases with follow-up <2 months were excluded from the evaluation. The median follow-up duration was 18.6 months. Seventeen patients received one PIT cycle, 14 received two, 6 received three, and 5 received four sessions. Among the 42 evaluable patients, 29 (69.0%) achieved a complete response (CR) lasting ≥2 months. Twenty patients remain alive with no evidence of disease. Disease-related deaths occurred in 3 patients, and 2 patients died from carotid artery rupture after treatment. Grade ≥3 adverse events were observed in 9 patients (21.4%). The 1-year overall survival rate was 89.7%. Among cases where pre-treatment blood samples were collected, 80% (4/5) showed elevated EBV-DNA levels on Cycle 1 Day 7, suggesting that EBV-DNA levels may reflect biological changes associated with PIT treatment. Conclusions: In this nationwide real-world cohort, PIT provided meaningful and long-lasting local control with a manageable safety profile for recurrent NPC. These findings support PIT as a clinically meaningful local treatment option for recurrent NPC and warrant further optimization of patient selection and risk mitigation strategies.