Department of Soft Tissue/Bone Sarcoma and Melanoma, Maria Sklodowska-Curie National Research Institute of Oncology, Roentgena 5, 02-781, Warsaw, Poland.
Medical University of Warsaw, Warsaw, Poland.
J Cancer Res Clin Oncol. 2023 Jul;149(7):2771-2782. doi: 10.1007/s00432-022-04149-0. Epub 2022 Jul 1.
Soft tissue sarcomas (STS) are diagnosed in 4-6 cases per 100 000 people a year and are associated with an unfavorable prognosis. Around one-third of patients will develop metastatic disease that requires palliative systemic therapy. Current therapeutic options have limited activity, and new treatments are tested, mainly in phase II trials. There is high variability and no standardization of phase II designs. We aimed to analyze the current landscape of phase II studies in STS and evaluate how its statistical design can affect the results.
Full-text phase II studies published in STS patients between 2005 and 2020 were identified and analyzed.
We have identified 102 trials, of which 77.4% were single-arm trials, 16.7% were randomized comparative trials (RCT), and 5.9% were randomized noncomparative trials. Including multiple cohorts, 22 randomized and 128 single-arm cohorts were analyzed. Nearly 80% of trials reported full statistical bases of the design. Over 20 different primary endpoints were used, with PFS as the most common in RCT trials (81.8%) and ORR (36.7%) and 3-months progression-free survival (PFS) rate (21.9%) in single-arm trials. Overall, 27.3% of RCT and 37.5% of single-arm trials were positive. Among single-arm trials, studies using 3- or 6-month rates were more often positive than those based on ORR.
There is high heterogeneity in sarcoma trial designs, mainly in primary-endpoint and hypotheses used for size calculation. There is an unmet need for standardization that will incorporate factors associated with the rarity of the disease, outcomes detected in previous trials and real-life studies, and specific characteristics of new therapeutic agents.
软组织肉瘤（STS）的年发病率为每 10 万人中有 4-6 例，预后不良。约有三分之一的患者会发展为转移性疾病，需要姑息性全身治疗。目前的治疗选择活性有限，正在测试新的治疗方法，主要是在 II 期临床试验中。II 期设计存在高度变异性且没有标准化。我们旨在分析 STS 中 II 期研究的现状，并评估其统计设计如何影响结果。
确定并分析了 2005 年至 2020 年期间发表的 STS 患者的 II 期研究全文。
我们共确定了 102 项试验，其中 77.4%为单臂试验，16.7%为随机对照试验（RCT），5.9%为随机非对照试验。包括多个队列，分析了 22 项随机和 128 项单臂队列。近 80%的试验报告了设计的完整统计基础。使用了 20 多种不同的主要终点，RCT 试验中最常见的是 PFS（81.8%），单臂试验中最常见的是 ORR（36.7%）和 3 个月无进展生存率（PFS）率（21.9%）。总体而言，27.3%的 RCT 和 37.5%的单臂试验为阳性。在单臂试验中，使用 3 个月或 6 个月的疗效评估的研究比基于 ORR 的研究更有可能为阳性。
肉瘤试验设计存在高度异质性，主要表现在主要终点和用于计算样本量的假设上。需要标准化，将与疾病罕见性、以前的试验和真实世界研究中检测到的结果以及新治疗药物的特定特征相关的因素纳入其中。
