Oncology Unit, Azienda Socio Sanitaria Territoriale (ASST) Bergamo Ovest, Treviglio, Italy.
Medical Oncology Unit, Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, Azienda Socio Sanitaria Territoriale (ASST) Spedali Civili of Brescia, Brescia, Italy.
Front Immunol. 2021 Sep 20;12:720748. doi: 10.3389/fimmu.2021.720748. eCollection 2021.
Rare cancers, as defined by the European Union, occur in fewer than 15 out of 100,000 people each year. The International Rare Cancer Consortium defines rare cancer incidence as less than six per 100,000 per year. There is a growing number of reports of the efficacy of immune checkpoint inhibitor (ICI) therapy in patients with rare tumours, and hence, we conducted a comprehensive review to summarise and analyse the available literature.
A literature search of PubMed was performed on January 31, 2021, using the following ICI names as keywords: ipilimumab, tremelimumab, cemiplimab, nivolumab, pembrolizumab, avelumab, atezolizumab, and durvalumab. Studies on patients with rare tumours who were being treated with ICIs were included. We plotted the overall response rate against the corresponding median survival across a variety of cancer types using linear regression.
From 1,255 publications retrieved during the primary search, 62 publications were selected (with a total of 4,620 patients). Only four were randomised trials. A minority were first-line studies, while the remaining were studies in which ICIs were delivered as salvage therapy in pretreated patients. There was a good correlation between response rate and overall survival (Spearman R >0.9) in skin cancers, mesothelioma, and sarcomas.
Treatment of advanced-stage rare tumours with ICI therapy was found to be associated with significant activity in some orphan diseases (e.g., Merkel cell carcinoma) and hepatocellular carcinoma. Several ongoing prospective clinical trials will expand the knowledge on the safety and efficacy of ICI therapy in patients with these rare cancers.
欧盟将罕见癌症定义为每年每 10 万人中少于 15 例的癌症。国际罕见癌症联合会将罕见癌症的发病率定义为每年每 10 万人少于 6 例。越来越多的报告表明免疫检查点抑制剂（ICI）治疗在罕见肿瘤患者中的疗效，因此，我们进行了全面的综述，以总结和分析现有文献。
于 2021 年 1 月 31 日在 PubMed 上进行了文献检索，使用以下 ICI 名称作为关键字：ipilimumab、tremelimumab、cemiplimab、nivolumab、pembrolizumab、avelumab、atezolizumab 和 durvalumab。纳入了接受 ICI 治疗的罕见肿瘤患者的研究。我们使用线性回归绘制了各种癌症类型的总体缓解率与相应的中位生存时间。
从初步搜索中检索到的 1255 篇文献中，选择了 62 篇文献（共 4620 名患者）。只有 4 项为随机试验。少数为一线研究，其余为 ICIs 作为预处理患者的挽救治疗的研究。在皮肤癌、间皮瘤和肉瘤中，缓解率与总生存率之间存在良好的相关性（Spearman R >0.9）。
ICI 治疗晚期罕见肿瘤与某些孤儿病（如 Merkel 细胞癌）和肝细胞癌的显著疗效相关。几项正在进行的前瞻性临床试验将扩大我们对这些罕见癌症患者使用 ICI 治疗的安全性和疗效的认识。
