Incidence of Cutaneous Immune-Related Adverse Events and Outcomes in Immune Checkpoint Inhibitor-Containing Regimens: A Systematic Review and Meta-Analysis.
Incidence of Cutaneous Immune-Related Adverse Events and Outcomes in Immune Checkpoint Inhibitor-Containing Regimens: A Systematic Review and Meta-Analysis.
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DOI：
10.3390/cancers16020340
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发表时间：
2024-01-13
期刊：
影响因子：
5.2
通讯作者：
Johnson, Douglas B.
中科院分区：
文献类型：
--
作者：
Curkovic, Nina B.;Bai, Kun;Ye, Fei;Johnson, Douglas B.
关键词：
免疫检查点抑制剂越来越多地用于治疗各种癌症，无论是单独还是与其他癌症疗法联合使用。副作用通常包括皮肤反应，这在由多种免疫检查点抑制剂组成的治疗方案中可能更频繁地发生。我们对临床试验进行了系统回顾和荟萃分析，以更好地了解几种不同免疫检查点抑制剂方案、剂量和癌症中继发于免疫检查点抑制剂的皮肤反应的频率，即皮肤免疫相关不良事件。我们的分析提供了皮肤免疫相关不良事件的基准发生率，包括瘙痒、皮疹和白癜风，并验证了先前报道的皮肤免疫相关不良事件的发展与治疗结果之间的联系。免疫检查点抑制剂（ICIs）用于治疗许多癌症，皮肤免疫相关不良事件（cirae）是最常见的毒性作用之一。随着cirae在不同环境、组合和肿瘤类型中的应用不断扩大，了解其发病率和预后相关性非常重要。为了评估cirae的发生率及其与各种ICI方案和癌症预后指标的相关性，我们对已发表的抗程序性死亡-1/配体-1 （PD-1/PD-L1）和抗细胞毒性T淋巴细胞抗原-4 (CTLA-4) ICIs的试验进行了系统回顾和荟萃分析，这些ICIs单独或与化疗、抗血管生成药物或其他ICIs联合用于黑色素瘤、肾细胞癌、非小细胞肺癌和尿路上皮癌患者。本研究的主要发现包括肿瘤和ICI方案中cirAE发病率的变化，与cirAE发病率和缓解率的增加呈正相关，以及白癜风发病率的增加与总生存期的显著相关。在174项研究中，皮疹、瘙痒和白癜风是报道最多的疾病，发病率分别为16.7%、18.0%和6.6%。与PD-1/L1单药治疗相比，较高的cirae发生率与ICI联合方案和含有ctla -4的方案相关，特别是与更高剂量的易普利姆单抗相关。包括缓解率和无进展生存期在内的结局指标与cirae的发生率呈正相关。瘙痒、白癜风和皮疹的缓解率和发病率分别与预期发病率上升相关，分别为0.17% （p = 0.0238）、0.40% （p = 0.0010）和0.18% （p = 0.0413）。总生存率与瘙痒、白癜风和皮疹的发生率呈正相关；这种关联在白癜风中是显著的（p = 0.0483）。我们的分析提供了cirae的基准发病率，并在不同实体肿瘤和多种ICI方案的研究水平上将cirae与有利的治疗结果联系起来。
Immune checkpoint inhibitors are increasingly being used in the treatment of a variety of cancers, both alone and in combination with other cancer therapies. Side effects often include skin reactions, which may occur more frequently in therapeutic regimens consisting of multiple immune checkpoint inhibitors. We conducted a systematic review and meta-analysis of clinical trials to better understand the frequency of skin reactions secondary to immune checkpoint inhibitors, known as cutaneous immune-related adverse events, across several different immune checkpoint inhibitor regimens, doses, and cancers. Our analysis provides benchmark incidence rates for cutaneous immune-related adverse events including pruritis, rash, and vitiligo, and validates previously reported links between the development of cutaneous immune-related adverse events and outcomes of therapy. 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.
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影响因子：
3.2
作者：
Chen, Yuh-Min;Yang, James Chih-Hsin;Yu, Chong-Jen
通讯作者：
Yu, Chong-Jen
影响因子：
4.7
作者：
Morgensztern D;Dols MC;Ponce Aix S;Postmus PE;Bennouna J;Fischer JR;Juan-Vidal O;Stewart DJ;Ardizzoni A;Bhore R;Wolfsteiner M;Reck M;Talbot D;Govindan R;Ong TJ
通讯作者：
Ong TJ
影响因子：
158.5
作者：
Choueiri, T. K.;Tomczak, P.;Powles, T.
通讯作者：
Powles, T.
DOI：
10.1111/1346-8138.15514
发表时间：
2020-11
期刊：
The Journal of dermatology
影响因子：
--
作者：
Namikawa K;Kiyohara Y;Takenouchi T;Uhara H;Uchi H;Yoshikawa S;Takatsuka S;Koga H;Wada N;Minami H;Hatsumichi M;Namba Y;Yamazaki N
通讯作者：
Yamazaki N
影响因子：
11.5
作者：
Carlino, Matteo S.;Menzies, Alexander M.;Long, Georgina, V
通讯作者：
Long, Georgina, V