抗血管生成药物联合PD⁃1抑制剂及化疗对晚期鼻咽癌的疗效与安全性分析
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1南京医科大学附属肿瘤医院(江苏省肿瘤医院)放疗科,江苏省肿瘤防治研究所,南京医科大学肿瘤个体化医学协同创新中心,江苏 南京 210009 ; 2.徐州医科大学研究生院,江苏 徐州 221000

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R739.63

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国家自然科学基金(82172804);江苏省卫健委重点项目(K2019028);南京市科技计划项目(2022SX00001663);南京医科大学鼻咽癌专病队列研究(NMUC2021011A)


Efficacy and safety of anti ⁃ angiogenic agents combined with PD ⁃ 1 inhibitors and chemotherapy in patients with recurrent or metastatic nasopharyngeal carcinoma
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1Department of Radiotherapy,the Affiliated Cancer Hospital of Nanjing Medical University,Jiangsu Cancer Hospital,Jiangsu Institute of Cancer Research,Collaborative Innovation Center for Cancer Personalized Medicine,NanjingMedical University,Nanjing 210009 ; 2.Postgraduate College,Xuzhou Medical University,Xuzhou 221000 ,China

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    摘要:

    目的:分析在程序性死亡受体1(programmed cell death protein 1,PD-1)抑制剂与化疗的基础上加入抗血管生成药物对非高发地区复发转移性鼻咽癌患者的近、远期疗效与安全性,以探索新的联合治疗方案。方法:对2019年1月—2024年12月在江苏省肿瘤医院经病理或影像学确认的171例复发或转移性鼻咽癌患者资料进行回顾性分析,其中接受抗血管生成药物联合 PD-1抑制剂+化疗为联合治疗组,PD-1抑制剂+化疗为非联合治疗组。收集患者基本临床资料、客观缓解率(objective response rate,ORR)、疾病控制率(disease control rate,DCR)、总生存期(overall survival,OS)、无进展生存期(progression-free survival,PFS) 以及治疗相关不良反应。卡方检验用于基线特征、近期疗效与不良反应发生率的组间比较,Kaplan-Meier 法计算生存率, log-rank检验比较生存差异,多因素Cox回归分析PFS相关预后因素并绘制森林图。结果:全组中位随访时间为31.7(2.8~61.8) 个月。联合治疗组的ORR(69.1%)显著优于非联合治疗组(49.5%)(P=0.011);联合治疗组的中位PFS为28.9个月,非联合治疗组为14.2个月(P=0.025);两组的OS差异无统计学意义(P=0.203)。亚组分析结果显示,联合治疗在年轻(≤50岁)、治疗前无贫血及肝转移、EB病毒(Epstein-Barr virus,EBV)DNA阳性、既往未接受免疫治疗且治疗线数≥2的患者中具有更显著的生存优势(P < 0.05)。另外,除皮疹和贫血外,两组的其他不良反应发生率无明显差异。结论:联合治疗在非高发区年轻、治疗前无贫血及肝转移、EBV-DNA阳性且一线化疗失败的复发转移性鼻咽癌患者中具有良好的抗肿瘤活性和安全性。

    Abstract:

    Objective:To evaluate the short-and long-term efficacy and safety of adding anti-angiogenic agents to programmed cell death protein 1(PD-1)inhibitors combined with chemotherapy in patients with recurrent or metastatic nasopharyngeal carcinoma(R/M NPC)from non-endemic regions,with the aim of exploring novel combination treatment strategies. Methods:A retrospective analysis was conducted on 171 patients with R/M NPC confirmed by pathology or imaging at Jiangsu Cancer Hospital between January 2019 and December 2024. Patients were divided into two groups:the combination group received anti-angiogenic agents plus PD-1 inhibitors and chemotherapy,while the non - combination group received PD - 1 inhibitors and chemotherapy alone. Clinical data including objective response rate(ORR),disease control rate(DCR),overall survival(OS),progression -free survival(PFS),and treatment - related adverse events were collected. The chi - square test was used to compare baseline characteristics,short - term efficacy,and adverse events between groups. Survival outcomes were analyzed using the Kaplan-Meier method and compared with the log-rank test. Prognostic factors for PFS were evaluated via multivariate Cox regression,and a forest plot was generated. Results:The median follow-up duration was 31.7(2.8-61.8)months. The ORR in the combination group was significantly higher than that in the non-combination group(69.1% vs. 49.5%,P = 0.011). The median PFS was 28.9 months in the combination group versus 14.2 months in the non - combination group(P=0.025). No statistically significant difference in OS was observed between the two groups(P=0.203). Subgroup analysis revealed that the survival benefit of combination therapy was more pronounced in patients aged ≤50 years,without pre - treatment anemia or liver metastasis,with positive EBV - DNA,and those who had not previously received immunotherapy or received ≥2 lines of therapy(P < 0.05). Apart from rash and anemia,the incidence of other adverse events did not differ significantly between the groups. Conclusion:Combination therapy exhibits favorable antitumor activity and an acceptable safety profile in nonendemic R/M NPC patients who are younger,have no pre-treatment anemia,are EBV-DNA positive,and failed first-line chemotherapy.

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高婧婧,宗丹,徐婧姝,何依月,何侠.抗血管生成药物联合PD⁃1抑制剂及化疗对晚期鼻咽癌的疗效与安全性分析[J].南京医科大学学报(自然科学版),2025,45(7):963-972

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  • 收稿日期:2025-02-07
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  • 在线发布日期: 2025-07-10
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