Real-word research on the effect and safety of gemcitabine combined with PD-1 inhibitors and recombinant human endostatin in refractory recurrent nasopharyngeal carcinoma.

e18016 Background: Recurrent nasopharyngeal carcinoma (rNPC) exhibits high heterogeneity, and conventional treatments often yield limited efficacy with significant toxicity. This study aimed to evaluate the safety and efficacy of a new regimen, GEP (Gemcitabine combined with recombinant human endostatin (Endostar) and PD-1 inhibitors), in patients with refractory rNPC in the real-world setting. Methods: Patients with refractory rNPC (recurrent lesions unsuitable for surgery or radical radiotherapy) treated at our hospital from December 2022 to October 2024 were retrospectively analyzed. All received GEP therapy comprising Gemcitabine (1.0 g/m² on days 1 and 8), Endostar (180-210 mg administered via continuous intravenous pump over 72-120 hours) and a PD-1 antibody. Selected patients also underwent low-dose radiotherapy (1 Gy x 3 fractions) and/or high-dose radiotherapy (5-8 Gy x 5 fractions) to the recurrent lesions. The objective response rate (ORR), disease control rate (DCR), and progression-free survival (PFS) were evaluated based on RECIST 1.1 criteria. Adverse events (AEs) were determined according to the CTCAE 5.0 version. Results: Twenty-four NPC patients staging III-IV who received ≥2 cycles of GEP were included (median age, 57.3 years). Among them, 54.1% had an ECOG performance status of 2 and 75% presented with comorbidities, such as heart disease, COPD. More than half of the patients had significant liquefaction necrosis (16/24) and ulceration (13/24) in recurrent lesions. 54.17% (13/24) of the patients were treated with more than second-line treatments before GEP. Five patients had received immunotherapy, and five had received targeted therapy previously. 45.8% (11/24) of the patients received low-dose radiotherapy, and 54.1% (13/24) received high-dose radiotherapy for recurrent nasopharyngeal tumors. The ORR and DCR were 66.7% and 87.5%, respectively. The PFS rates at 12 months and 30 months were 80.07% and 62.28%, respectively. In the safety analysis set, adverse events (AEs) above Grade 3 included hematological toxicity (5/24), nausea (1/24), and liver dysfunction (1/24). Other grade 1-2 AEs were hemorrhage (5/24), infusion reaction (3/31), skin pruritus (3/24), cardiotoxicity (2/24), weight loss (13/24), abdominal distension, and constipation (10/24). The significant factors associated with ORR were radiotherapy (p=0.020) and high-dose radiotherapy (p=0.018). The correlation factors associated with PFS were liquefaction necrosis (p=0.032), radiotherapy (p=0.005) and high-dose radiotherapy (p=0.003). Conclusions: Real-world data demonstrated that GEP was well-tolerated and effective in patients with refractory recurrent NPC. Radiotherapy, especially high-dose radiotherapy may contribute to ORR and PFS. Clinical trial information: NCT06611826 .