Reporting of post-protocol therapies in metastatic breast cancer registration clinical trials: A systematic review

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.