Orlandi Elena, Guasconi Massimo, Romboli Andrea, Giuffrida Mario, Toscani Ilaria, Anselmi Elisa, Porzio Rosa, Madaro Serena, Vecchia Stefano, Citterio Chiara
Department of Oncology-Hematology, Azienda USL of Piacenza, 29121 Piacenza, Italy.
Department of Medicine and Surgery, University of Parma, 43121 Parma, Italy.
Int J Mol Sci. 2025 Mar 14;26(6):2620. doi: 10.3390/ijms26062620.
Immune checkpoint inhibitors (ICIs) have transformed the therapeutic landscape for several malignancies, but their efficacy in unresectable pancreatic adenocarcinoma remains uncertain. This systematic review aimed to evaluate the effectiveness and safety of ICIs in this context, focusing on overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and toxicity. A comprehensive search of MEDLINE, EMBASE, CENTRAL, and Scopus identified 34 eligible studies, including randomized controlled trials and observational cohorts. Quantitative synthesis involved 21 studies comprising 937 patients, with additional qualitative analyses on biomarker-driven subgroups and early-phase trials. The median OS across studies was 8.65 months, while the median PFS was 2.55 months. The ORR and DCR were 16.2% and 50.3%, respectively, with grade ≥3 treatment-related adverse events occurring in 22% of patients. Promising outcomes were observed in MSI-H/dMMR populations, although these represented only 1-2% of cases. Combination strategies with chemotherapy demonstrated synergistic potential but lacked definitive evidence due to heterogeneity and the absence of phase III trials. ICIs showed a manageable toxicity profile, highlighting their feasibility in selected patients. Future research should focus on overcoming tumor microenvironment barriers and identifying biomarkers to optimize responsiveness and expand the applicability of ICIs in pancreatic cancer.
免疫检查点抑制剂（ICIs）已经改变了几种恶性肿瘤的治疗格局，但其在不可切除的胰腺腺癌中的疗效仍不确定。本系统评价旨在评估ICIs在此背景下的有效性和安全性，重点关注总生存期（OS）、无进展生存期（PFS）、客观缓解率（ORR）、疾病控制率（DCR）和毒性。对MEDLINE、EMBASE、CENTRAL和Scopus进行全面检索，确定了34项符合条件的研究，包括随机对照试验和观察性队列研究。定量综合分析涉及21项研究，共937例患者，并对生物标志物驱动的亚组和早期试验进行了额外的定性分析。各研究的中位OS为8.65个月，中位PFS为2.55个月。ORR和DCR分别为16.2%和50.3%，22%的患者发生≥3级治疗相关不良事件。在微卫星高度不稳定/错配修复缺陷（MSI-H/dMMR）人群中观察到了有前景的结果，尽管这些人群仅占病例的1%-2%。与化疗的联合策略显示出协同潜力，但由于异质性和缺乏III期试验，缺乏确凿证据。ICIs显示出可控制的毒性特征，突出了其在特定患者中的可行性。未来的研究应集中在克服肿瘤微环境障碍和识别生物标志物，以优化反应性并扩大ICIs在胰腺癌中的适用性。
