Immune checkpoint inhibitors (ICIs) are used to treat many cancers, and cutaneous immune-related adverse events (cirAEs) are among the most frequently encountered toxic effects. Understanding the incidence and prognostic associations of cirAEs is of importance as their uses in different settings, combinations, and tumor types expand. To evaluate the incidence of cirAEs and their association with outcome measures across a variety of ICI regimens and cancers, we performed a systematic review and meta-analysis of published trials of anti–programmed death-1/ligand-1 (PD-1/PD-L1) and anti–cytotoxic T lymphocyte antigen-4 (CTLA-4) ICIs, both alone and in combination with chemotherapy, antiangiogenic agents, or other ICIs in patients with melanoma, renal cell carcinoma, non-small cell lung cancer, and urothelial carcinoma. Key findings of our study include variable cirAE incidence among tumors and ICI regimens, positive association with increased cirAE incidence and response rate, as well as significant association between increased vitiligo incidence and overall survival. Across 174 studies, rash, pruritis, and vitiligo were the most reported cirAEs, with incidences of 16.7%, 18.0%, and 6.6%, respectively. Higher incidence of cirAEs was associated with ICI combination regimens and with CTLA-4-containing regimens, particularly with higher doses of ipilimumab, as compared to PD-1/L1 monotherapies. Outcome measures including response rate and progression-free survival were positively correlated with incidence of cirAEs. The response rate and incidence of pruritis, vitiligo, and rash were associated with expected rises in incidence of 0.17% (p= 0.0238), 0.40% (p= 0.0010), and 0.18% (p= 0.0413), respectively. Overall survival was positively correlated with the incidence of pruritis, vitiligo, and rash; this association was significant for vitiligo (p= 0.0483). Our analysis provides benchmark incidence rates for cirAEs and links cirAEs with favorable treatment outcomes at a study level across diverse solid tumors and multiple ICI regimens.
免疫检查点抑制剂（ICIs）已广泛应用于多种癌症的治疗，其中皮肤免疫相关不良事件（cirAEs）是最常见的毒性反应之一。随着ICIs在不同治疗场景、联合方案及肿瘤类型中的应用日益扩展，明确cirAEs的发生率及其与预后的关联具有重要意义。为评估不同ICI方案及癌症类型中cirAEs的发生率及其与疗效指标的关联，我们对已发表的抗程序性死亡受体-1/配体-1（PD-1/PD-L1）及抗细胞毒性T淋巴细胞抗原-4（CTLA-4）ICI临床试验进行了系统综述与荟萃分析。这些试验涵盖单药治疗及与化疗、抗血管生成药物或其他ICIs的联合方案，涉及黑色素瘤、肾细胞癌、非小细胞肺癌和尿路上皮癌患者。研究核心发现包括：cirAE发生率因肿瘤类型和ICI方案而异；cirAE发生率升高与治疗反应率呈正相关；白癜风发生率与总生存期显著相关。在纳入的174项研究中，皮疹、瘙痒和白癜风是最常报告的cirAEs，发生率分别为16.7%、18.0%和6.6%。与PD-1/L1单药治疗相比，ICI联合方案及含CTLA-4的方案（尤其是高剂量伊匹木单抗）的cirAE发生率更高。疗效指标包括反应率和无进展生存期与cirAE发生率呈正相关。瘙痒、白癜风和皮疹的发生率每增加1%，预期反应率分别相应升高0.17%（p=0.0238）、0.40%（p=0.0010）和0.18%（p=0.0413）。总生存期与瘙痒、白癜风和皮疹发生率呈正相关，其中白癜风的相关性具有统计学意义（p=0.0483）。本分析为cirAEs提供了基准发生率数据，并在研究层面证实了cirAEs与多种实体瘤及不同ICI方案的良好治疗结局存在关联。
肿瘤(癌症)患者之家