e18061 Background: For unresectable locally rNPC patients, re-irradiation with intensity-modulated radiotherapy remains the standard approach, despite its survival and safety limitations. We designed a prospective clinical trial to explore the efficacy and safety of tislelizumab combined with chemotherapy for unresectable recurrent locally advanced NPC patients. Methods: This was a prospective, single-arm, open-label phase II clinical trial. The key inclusion criteria were patients aged 14 to 75 years with histologically confirmed locally recurrent rII-IVA (rT3-4N0-2M0) nasopharyngeal carcinoma occurring more than 12 months after completion of definitive primary treatment. Eligible participants were with medically unresectable tumor or had residual disease after surgery. Participants were required to have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Patients were excluded if they had received any prior radiotherapy, systemic therapy. All patients initially received 4 cycles of combination therapy comprising tislelizumab (200 mg, d1, Q3W) plus investigator-determined chemotherapy regimens. Radiological tumor assessments were performed every 6 weeks by RECIST v1.1. Patients demonstrating objective response (complete or partial response) or stable disease continued treatment with tislelizumab monotherapy maintenance (200 mg every 3 weeks or 400 mg every 6 weeks). In cases of documented disease progression, patients were transitioned to salvage re-irradiation with intensity-modulated radiation therapy. Results: Between the March 2021 and March 2024, a total of 20 eligible patients were enrolled in this study. By the time of December 30, 2025, the median follow-up duration was 39.0 months (range: 15.2-51.8 months). The median progression-free survival was not reached (95% CI: 9.4, NR). The 1-year PFS rate was 77.3% (95% CI: 49.6%-91.0%), and the 2-year PFS rate was 70.3% (95% CI: 41.9%-86.7%). All adverse events were graded according to the CTCAE v5.0. The treatment demonstrated a favorable safety profile overall. 18 (90%) experienced at least one treatment-emergent adverse event (TEAE), with the majority being grade 1-2 events that were clinically manageable. Conclusions: Our study establishes tislelizumab combined with chemotherapy as a feasible and effective treatment strategy for unresectable recurrent locally advanced NPC. The sequential approach demonstrates promising efficacy with manageable toxicity, offering a potential paradigm shift in the management of this challenging patient population. These results support the continued investigation of immunotherapy-based strategies in recurrent NPC and highlight the importance of innovative treatment sequencing in optimizing outcomes.
Wang et al. (Thu,) studied this question.