Colomer-Lahiguera Sara, Bryant-Lukosius Denise, Rietkoetter Sarah, Martelli Lorraine, Ribi Karin, Fitzpatrick-Lewis Donna, Sherifali Diana, Orcurto Angela, Juergens Rosalyn, Eicher Manuela
Institute of Higher Education and Research in Healthcare (IUFRS), Faculty of Biology and Medicine, University of Lausanne, Lausanne, Switzerland.
Department of Oncology, Lausanne University Hospital (CHUV), Lausanne, Switzerland.
J Patient Rep Outcomes. 2020 Jul 16;4(1):58. doi: 10.1186/s41687-020-00210-z.
Immune-checkpoint inhibitors (ICI) have shown significant benefits for overall survival across various cancer types. Patient-reported outcomes (PROs) are assessed in clinical trials as a measure of efficacy. However, it remains unclear to what extent current PRO instruments capture symptoms specific to ICI toxicities. We conducted a systematic review to identify the use and content validity of PRO instruments in ICI clinical trials in oncology.
Literature was retrieved from PubMed, Embase, PsycINFO, Medline and CINAHL databases. Articles presenting ICI clinical trials' PRO results, clinical trial study protocols, and conference abstracts stating the use of PRO measures were assessed. We evaluated the validity of identified instruments by comparing their symptom-related content with the adverse events reported in each ICI clinical trial.
From database inception until January 2020, we identified 191 ICI clinical trials stating the use of PRO measures of which 26 published PRO results. The cancer-specific EORTC QLQ-C30 and the generic EQ-5D questionnaires were the most widely used instruments, often in combination with disease-specific PROs. Instruments used to report PRO symptom-related toxicities covered 45% of the most frequently reported AEs, whereas 23% of AEs were partially covered and 29% were not covered at all. Of non-covered AEs, 59% referred to the dermatologic system. Partially covered AEs related to endocrine and specific types of pain.
Despite the high frequency of symptom-related toxicities related to ICI, these events are only partially covered (or not addressed) by current PRO instruments, even when combined. Further research is needed to develop new strategies to tailor PRO instruments to specific ICI toxicities.
免疫检查点抑制剂（ICI）已在多种癌症类型中显示出对总生存期有显著益处。在临床试验中评估患者报告结局（PRO）作为疗效的一种衡量指标。然而，目前的PRO工具在多大程度上能够捕捉ICI毒性特有的症状仍不清楚。我们进行了一项系统评价，以确定PRO工具在肿瘤学ICI临床试验中的使用情况和内容效度。
从PubMed、Embase、PsycINFO、Medline和CINAHL数据库中检索文献。对呈现ICI临床试验PRO结果、临床试验研究方案以及说明使用PRO测量方法的会议摘要的文章进行评估。我们通过将已识别工具中与症状相关的内容与每个ICI临床试验中报告的不良事件进行比较，来评估这些工具的效度。
从数据库建立到2020年1月，我们识别出191项说明使用PRO测量方法的ICI临床试验，其中26项发表了PRO结果。癌症特异性的欧洲癌症研究与治疗组织核心问卷（EORTC QLQ-C30）和通用的EQ-5D问卷是使用最广泛的工具，通常与疾病特异性的PRO一起使用。用于报告与PRO症状相关毒性的工具涵盖了45%最常报告的不良事件，而23%的不良事件被部分涵盖，29%的不良事件完全未被涵盖。在未被涵盖的不良事件中，59%涉及皮肤系统。部分被涵盖的不良事件与内分泌和特定类型的疼痛有关。
尽管与ICI相关的症状性毒性发生率很高，但目前的PRO工具即使联合使用也只能部分涵盖（或未涉及）这些事件。需要进一步研究来制定新策略，使PRO工具能够针对特定的ICI毒性进行定制。
