Edinburgh Cancer Research Centre, University of Edinburgh, Edinburgh, UK.
St Columba's Hospice, Edinburgh, UK.
J Cachexia Sarcopenia Muscle. 2023 Oct;14(5):1932-1948. doi: 10.1002/jcsm.13321. Epub 2023 Sep 6.
In cancer cachexia trials, measures of physical function are commonly used as endpoints. For drug trials to obtain regulatory approval, efficacy in physical function endpoints may be needed alongside other measures. However, it is not clear which physical function endpoints should be used. The aim of this systematic review was to assess the frequency and diversity of physical function endpoints in cancer cachexia trials. Following a comprehensive electronic literature search of MEDLINE, Embase and Cochrane (1990-2021), records were retrieved. Eligible trials met the following criteria: adults (≥18 years), controlled design, more than 40 participants, use of a cachexia intervention for more than 14 days and use of a physical function endpoint. Physical function measures were classified as an objective measure (hand grip strength [HGS], stair climb power [SCP], timed up and go [TUG] test, 6-min walking test [6MWT] and short physical performance battery [SPPB]), clinician assessment of function (Karnofsky Performance Status [KPS] or Eastern Cooperative Oncology Group-Performance Status [ECOG-PS]) or patient-reported outcomes (physical function subscale of the European Organisation for the Research and Treatment of Cancer Quality of Life Questionnaires [EORTC QLQ-C30 or C15]). Data extraction was performed using Covidence and followed PRISMA guidance (PROSPERO registration: CRD42022276710). A total of 5975 potential studies were examined and 71 were eligible. Pharmacological interventions were assessed in 38 trials (54%). Of these, 11 (29%, n = 1184) examined megestrol and 5 (13%, n = 1928) examined anamorelin; nutritional interventions were assessed in 21 trials (30%); and exercise-based interventions were assessed in 6 trials (8%). The remaining six trials (8%) assessed multimodal interventions. Among the objective measures of physical function (assessed as primary or secondary endpoints), HGS was most commonly examined (33 trials, n = 5081) and demonstrated a statistically significant finding in 12 (36%) trials (n = 2091). The 6MWT was assessed in 12 trials (n = 1074) and was statistically significant in 4 (33%) trials (n = 403), whereas SCP, TUG and SPPB were each assessed in 3 trials. KPS was more commonly assessed than the newer ECOG-PS (16 vs. 9 trials), and patient-reported EORTC QLQ-C30 physical function was reported in 25 trials. HGS is the most commonly used physical function endpoint in cancer cachexia clinical trials. However, heterogeneity in study design, populations, intervention and endpoint selection make it difficult to comment on the optimal endpoint and how to measure this. We offer several recommendations/considerations to improve the design of future clinical trials in cancer cachexia.
在癌症恶病质试验中，身体功能的测量通常被用作终点。为了获得药物试验的监管批准，除了其他措施外，身体功能终点的疗效可能也是必要的。然而，目前还不清楚应该使用哪些身体功能终点。本系统评价的目的是评估癌症恶病质试验中身体功能终点的频率和多样性。通过对 MEDLINE、Embase 和 Cochrane（1990-2021 年）进行全面的电子文献检索，检索到记录。符合条件的试验符合以下标准：成年人（≥18 岁）、对照设计、超过 40 名参与者、使用恶病质干预措施超过 14 天、使用身体功能终点。身体功能测量分为客观测量（握力[HGS]、爬楼梯功率[SCP]、计时起立行走测试[TUG]、6 分钟步行测试[6MWT]和短程体能表现电池[SBBP]）、临床医生评估的功能（卡氏绩效状态[KPS]或东部合作肿瘤学组绩效状态[ECOG-PS]）或患者报告的结局（欧洲癌症研究与治疗组织生活质量问卷[EORTC QLQ-C30 或 C15]的身体功能子量表）。使用 Covidence 进行数据提取，并遵循 PRISMA 指南（PROSPERO 注册：CRD42022276710）。共检查了 5975 项潜在研究，其中 71 项符合条件。评估了 38 项药理学干预试验（54%）。其中，11 项（29%，n=1184）检查了美曲孕酮，5 项（13%，n=1928）检查了 anamorelin；评估了 21 项营养干预试验（30%）；评估了 6 项基于运动的干预试验（8%）。其余 6 项试验（8%）评估了多模式干预。在身体功能的客观测量中（作为主要或次要终点进行评估），HGS 最常被评估（33 项试验，n=5081），在 12 项（36%）试验（n=2091）中显示出统计学意义的发现。6MWT 评估了 12 项试验（n=1074），其中 4 项（33%）试验（n=403）具有统计学意义，而 SCP、TUG 和 SPPB 各评估了 3 项。KPS 的评估比新型 ECOG-PS 更常见（16 项与 9 项试验），25 项试验报告了患者报告的 EORTC QLQ-C30 身体功能。HGS 是癌症恶病质临床试验中最常用的身体功能终点。然而，研究设计、人群、干预措施和终点选择的异质性使得很难评论最佳终点以及如何衡量这一点。我们提出了一些建议/考虑因素，以改善癌症恶病质未来临床试验的设计。
