Li Wanpeng, Wang Tian, Xu Haoyuan, Liu Quan, Zhang Huankang, Yang Yufei, Sun Xicai, Yu Huapeng, Gu Yurong, Li Houyong, Ding Hao, Wang Dehui
ENT Institute and Department of Otorhinolaryngology, Eye and ENT Hospital, Fudan University, Shanghai, China.
Department of Radiation Oncology, Eye Ear Nose and Throat Hospital of Fudan University, Shanghai, China.
J Immunother Cancer. 2025 May 24;13(5):e011998. doi: 10.1136/jitc-2025-011998.
Endoscopic surgery has become the first-line treatment for surgically resectable recurrent nasopharyngeal carcinoma (rNPC), but it is associated with a high risk of postoperative tumor progression. Currently, there is a lack of effective and well-tolerated adjuvant treatment regimens. Thus, the primary objective was to investigate the efficacy and safety of tislelizumab as adjuvant therapy with endoscopic surgery for the treatment of patients with rNPC.
This was a single-center, open-label, randomized, controlled, phase 2 trial between November 23, 2021, and May 8, 2024. Eligible patients included those with complete tumor disappearance as indicated by postoperative imaging, histopathologically diagnosed with undifferentiated or differentiated non-keratinizing rNPC. Patients with rNPC were randomized to receive endoscopic surgery alone or adjuvant tislelizumab treatment 2-6 weeks after endoscopic surgery. Tislelizumab was administered as a 200 mg intravenous infusion every 3 weeks until disease progression, death, unacceptable toxicity, withdrawal of consent, investigator's decision, or 1 year. The primary endpoint was progression-free survival (PFS) at 1 year, and secondary endpoints included 1-year progression-free interval (PFI), 1-year overall survival (OS), and safety.
The trial is ongoing. 42 patients were enrolled at a median follow-up of 18 months (IQR 10-27), the 1-year PFS was significantly higher in the tislelizumab group (94%, 95% CI: 83% to 100%) than in the endoscopic surgery alone group (57%, 95% CI: 38% to 85%). The 1-year PFI was also higher in the tislelizumab group (100%, 95% CI: 100% to 100%) than in the endoscopic surgery alone group (60%, 95% CI: 40% to 89%). No significant difference in the 1-year OS was observed at the data cut-off. Grade ≥3 immune-related adverse events (irAEs) occurred in 9% of tislelizumab recipients, and all of these events were elevated blood creatine phosphokinase levels. Additionally, the most common irAEs in this group were hypothyroidism, affecting 27%, and pruritus, observed in 9%.
Tislelizumab as adjuvant therapy significantly enhanced PFS and PFI, with a favorable safety profile. Longer follow-up is necessary to determine whether this regimen can be considered as the standard of care for patients with resectable rNPC following endoscopic surgery.
NCT05092217.
内镜手术已成为可手术切除的复发性鼻咽癌（rNPC）的一线治疗方法，但术后肿瘤进展风险较高。目前，缺乏有效且耐受性良好的辅助治疗方案。因此，主要目的是研究替雷利珠单抗作为内镜手术辅助治疗rNPC患者的疗效和安全性。
这是一项单中心、开放标签、随机、对照的2期试验，时间为2021年11月23日至2024年5月8日。符合条件的患者包括术后影像学显示肿瘤完全消失、经组织病理学诊断为未分化或分化型非角化性rNPC的患者。rNPC患者被随机分为单纯接受内镜手术或在内镜手术后2 - 6周接受辅助替雷利珠单抗治疗。替雷利珠单抗每3周静脉输注200mg，直至疾病进展、死亡、出现不可接受的毒性、撤回同意、研究者决定或满1年。主要终点是1年无进展生存期（PFS），次要终点包括1年无进展间期（PFI）、1年总生存期（OS）和安全性。
试验正在进行中。42例患者入组，中位随访18个月（四分位间距10 - 27个月），替雷利珠单抗组的1年PFS（94%，95%CI：83%至100%）显著高于单纯内镜手术组（57%，95%CI：38%至85%）。替雷利珠单抗组的1年PFI（100%，95%CI：100%至100%）也高于单纯内镜手术组（60%，95%CI：40%至89%）。在数据截止时，未观察到1年OS有显著差异。9%接受替雷利珠单抗治疗的患者发生了≥3级免疫相关不良事件（irAE），所有这些事件均为血肌酸磷酸激酶水平升高。此外，该组最常见的irAE是甲状腺功能减退，发生率为27%，瘙痒发生率为9%。
替雷利珠单抗作为辅助治疗可显著提高PFS和PFI，安全性良好。需要更长时间的随访来确定该方案是否可被视为内镜手术后可切除rNPC患者的标准治疗方案。
NCT05092217。
