Department of Oncology, Geneva University Hospital, 4 Gabrielle-Perret-Gentil Street, Geneva, 1205, Switzerland.
Department of Epidemiology and Biostatistics, University of California San Francisco, 550 16th St, 2nd Fl, San Francisco, CA, 94158, USA.
BMC Cancer. 2023 May 17;23(1):448. doi: 10.1186/s12885-023-10917-z.
Suboptimal treatment upon progression may affect overall survival (OS) results in oncology randomized controlled trials (RCTs). We aim to assess the proportion of trials reporting post-progression treatment.
This cross-sectional analysis included two concurrent analyses. The first one examined all published RCTs of anti-cancer drugs in six high impact medical/oncology journals between January 2018 and December 2020. The second studied all US Food and Drug Administration (FDA) approved anti-cancer drugs during the same period. Included trials needed to study an anti-cancer drug in the advanced or metastatic setting. Data abstracted included the tumor type, characteristics of trials, and reporting and assessment of post-progression treatment.
There were 275 published trials and 77 US FDA registration trials meeting inclusion criteria. Assessable post-progression data were reported in 100/275 publications (36.4%) and 37/77 approvals (48.1%). Treatment was considered substandard in 55 publications (n = 55/100, 55.0%) and 28 approvals (n = 28/37, 75.7%). Among trials with assessable post-progression data and positive OS results, a subgroup analysis identified substandard post-progression treatment in 29 publications (n = 29/42, 69.0%) and 20 approvals (n = 20/26, 76.9%). Overall, 16.4% of publications (45/275) and 11.7% of registration trials (9/77) had available post-progression data assessed as appropriate.
We found that most anti-cancer RCTs do not report assessable post-progression treatment. When reported, post-progression treatment was substandard in most trials. In trials reporting positive OS results and with assessable post-progression data, the proportion of trials with subpar post-progression treatment was even higher. Discrepancies between post-progression therapy in trials and the standard of care can limit RCT results' applicability. Regulatory rules should enforce higher requirements regarding post-progression treatment access and reporting.
进展后治疗选择不当可能会影响肿瘤学随机对照试验（RCT）的总生存期（OS）结果。我们旨在评估报告进展后治疗的试验比例。
这项横断面分析包括两个同时进行的分析。第一个分析检查了 2018 年 1 月至 2020 年 12 月期间六本高影响力医学/肿瘤学期刊上发表的所有抗癌药物的 RCT。第二个分析研究了同期所有获得美国食品和药物管理局（FDA）批准的抗癌药物。纳入的试验需要研究晚期或转移性癌症的抗癌药物。提取的数据包括肿瘤类型、试验特征以及进展后治疗的报告和评估。
有 275 项发表的试验和 77 项美国 FDA 注册试验符合纳入标准。在 275 项出版物中有 100 项（36.4%）和 77 项美国 FDA 注册中有 37 项（48.1%）报告了可评估的进展后数据。在 55 项出版物（n=55/100，55.0%）和 28 项美国 FDA 注册中有 28 项（n=28/37，75.7%）中，治疗被认为不达标。在有可评估的进展后数据和阳性 OS 结果的试验中，亚组分析发现，在 29 项出版物（n=29/42，69.0%）和 20 项美国 FDA 注册中有 20 项（n=20/26，76.9%）中存在不达标进展后治疗。总体而言，275 项出版物中有 16.4%（45/275）和 77 项美国 FDA 注册中有 11.7%（9/77）有可用的进展后数据进行了评估。
我们发现大多数抗癌 RCT 未报告可评估的进展后治疗。当报告时，大多数试验中的进展后治疗不达标。在报告阳性 OS 结果和可评估的进展后数据的试验中，治疗效果不佳的试验比例更高。试验中进展后治疗与标准治疗之间的差异可能会限制 RCT 结果的适用性。监管规则应提高对进展后治疗获得和报告的要求。
