新辅助抗PD-1/PD-L1在可手术切除的头颈部鳞状细胞癌中的疗效及安全性分析与评价

Analysis and evaluation of the efficacy and safety of neoadjuvant anti-PD-1/PD-L1 in resectable head and neck squamous cell carcinoma

摘要:

目的 系统评价新辅助抗程序性死亡受体1(PD-1)或程序性死亡受体配体1(PD-L1)在可手术切除的头颈部鳞状细胞癌(HNSCC)患者中的疗效与安全性，为临床治疗提供参考。方法 检索PubMed、Embase、Cochrane Library和Web of science等数据库从建库至 2023年11月前发表的研究，按照纳入及排除标准筛选文献，采用 JBI评价工具对文献进行质量评价，并应用Revman 5.4进行单臂Meta 分析。结果 共纳入15篇文献、496例患者。Meta分析结果显示：患者疾病客观缓解率为39%(95%CI：29%~54%)，病理学缓解率为55%(95%CI：48%~63%)，1年无进展生存率为84%(95%CI:75%~ 95%)，1年总体生存率为86%(95%CI:78%~ 95%)，患者的3级及以上不良反应的发生率为20%(95%CI：13%~31%)。12项研究报道了与治疗相关的手术延迟情况，仅有1项研究中出现1例患者因免疫治疗而延误原定手术时间。亚组分析比较了单用抗PD-1/PD-L1、双免疫检查点抑制剂、抗PD-1/PD-L1+放射治疗、抗PD-1/PD-L1+化学疗法及抗PD-1/PD-L1+基因靶向治疗的疗效及安全性，结果显示，这5种不同治疗方案之间的病理学缓解率和安全性差异无统计学意义，抗PD-1/PD-L1+基因靶向治疗组的客观缓解率(13%，95%CI：5%~37%)最低，抗PD-1/PD-L1+化学疗法的客观缓解率(90%，95%CI：75%~107%)最高，另3组治疗方案间的客观缓解率差异无统计学意义。结论 在本荟萃分析和系统回顾中，新辅助抗PD-1/PD-L1免疫治疗对可切除的HNSCC耐受性良好，可能具有组织病理学反应所暗示的治疗优势。在抗PD-1/PD-L1联合或不联合其他辅助治疗的方案中，抗PD-1/PD-L1联合化学疗法的客观缓解率较其他组合治疗组更高，期待更多的临床研究来探索长期疗效和最佳治疗组合。

关键词:头颈部鳞状细胞癌;新辅助;抗PD-1/PD-L1;Meta分析;手术

Abstract:

Objective To systematically evaluate the efficacy and safety of neoadjuvant programmed cell death 1 (PD-1)/programmed cell death 1 ligand (PD-L1) in patients with resectable head and neck squamous cell carcinoma (HNSCC), so as to provide reference for clinical treatment.Methods Studies published before November 2023 were retrieved from PubMed, Embase, Cochrane Library and Web of science databases, and literatures were screened according to inclusion and exclusion criteria. Joanna Briggs Institute (JBI) evaluation tool was used to evaluate the quality of literatures. Moreover, Revman 5.4 was used to conduct a one-arm Meta analysis.Results A total of 15 literatures and 496 patients were included. The results of Meta analysis showed that objective disease response rate was 39%[95% confidence interval (95%CI)：29%-54%], pathological response rate was 55% (95%CI：48%-63%), 1-year progression-free survival rate was 84% (95%CI:75%-95%), and 1-year overall survival rate was 86% (95%CI:78%-95%). The incidence of grade 3 or higher adverse events was 20% (95%CI: 13%-31%). Treatment-related surgical delays were reported in 12 studies, with only one patient delayed due to immunotherapy in one study. Subgroup analysis compared the efficacy and safety of anti-PD-1/PD-L1 alone, dual immune checkpoint inhibitors, anti-PD-1/PD-L1+radiation therapy, anti-PD-1/PD-L1+chemotherapy and anti-PD-1/PD-L1+gene targeted drug. There were no statistical differences in pathological response rate and safety among the five different treatment regimens. Anti-PD-1/PD-L1+gene-targeted drug group had the lowest objective response rate (13%, 95%CI: 5%-37%), and anti-PD-1/PD-L1+chemotherapy had the highest objective response rate (90%, 95%CI: 75%-107%). There were no significant differences in the objective response rate among the other three treatment regimens.Conclusion In this Meta-analysis and systematic review, neoadjuvant anti-PD-1/PD-L1 immunotherapy is well tolerated in resectable HNSCC and may have therapeutic advantages implied by histopathological responses. In the anti-PD-1/PD-L1 regimen with or without other adjuvant therapy, the objective response rate of anti-PD-1/PD-L1 combined chemotherapy is higher than those of other combination treatment groups, and more clinical studies are expected to explore long-term efficacy and the optimal treatment combination.

Key words:Head and neck squamous cell carcinoma;Neoadjuvant;Anti-PD-1/PD-L1;Meta analysis;Surgery