Background

As the treatment for metastatic breast cancer (MBC) often includes sequential lines of therapy, data on post-protocol treatment in clinical trials are valuable in the assessment of long-term outcomes. The objective of this study was to assess the reported data on post-protocol therapy in clinical trials supporting US Food and Drug Administration (FDA) approval of drugs for MBC.

Methods

All initial and subsequent publications related to FDA approved indications for MBC between January 2000 and February 2023 were identified. Collected data included study design, patients' characteristics and whether reporting on post-protocol therapy was available. Differences in study design and population between studies with and without data on post-protocol therapy were evaluated.

Findings:

Forty-one indications for MBC were identified. Data were evaluated from 249 publications or abstracts, comprising 20,152 patients. Reporting of post-protocol therapy was available for 22 (53.7 %) indications. Reported data were often incomplete. Reporting has not improved over time with reported data in 50 % and 55.2 % studies between 2000 and 2010 and 2011–2023 (p value for the difference = 1.0), respectively. Studies with OS as their primary endpoints were associated with significantly higher reporting of post-protocol therapy, (p = 0.02). Other characteristics of study design and population were comparable between studies with and without data on post-protocol therapy.

Conclusions

Data on post-protocol therapy in trials supporting FDA approval of drugs for MBC are available for only half of the indications. As subsequent lines of therapy may have a crucial role in patients' outcome, post-protocol reporting should be included in the regulatory submission and be made available publicly.

中文翻译：

---

转移性乳腺癌注册临床试验中方案后治疗的报告：系统评价

背景

由于转移性乳腺癌 (MBC) 的治疗通常包括序贯治疗，因此临床试验中方案后治疗的数据对于评估长期结果非常有价值。本研究的目的是评估支持美国食品和药物管理局 (FDA) 批准 MBC 药物的临床试验中方案后治疗的报告数据。

方法

确定了 2000 年 1 月至 2023 年 2 月期间与 FDA 批准的 MBC 适应症相关的所有初始和后续出版物。收集的数据包括研究设计、患者特征以及是否可以获得方案后治疗的报告。对有和没有方案后治疗数据的研究之间的研究设计和人群差异进行了评估。

发现：

确定了 41 种 MBC 适应症。数据评估来自 249 份出版物或摘要，涉及 20,152 名患者。22 种适应症 (53.7%) 可获得方案后治疗的报告。报告的数据常常不完整。随着时间的推移，报告并没有得到改善，2000 年至 2010 年以及 2011 年至 2023 年期间分别有 50% 和 55.2% 的研究报告了数据（差异 p 值 = 1.0）。以 OS 作为主要终点的研究与显着较高的方案后治疗报告相关 (p = 0.02)。有或没有方案后治疗数据的研究之间的研究设计和人群的其他特征具有可比性。

结论

支持 FDA 批准 MBC 药物的试验中的方案后治疗数据仅适用于一半的适应症。由于后续的治疗方案可能对患者的结果起着至关重要的作用，因此方案后报告应包含在监管提交中并公开发布。