Trends in endpoint use in pivotal trials and efficacy for US Food and Drug Administration-approved solid tumor therapies, 1995-2021.

Abstract

BACKGROUND: Many cancer therapies are now approved based on surrogate endpoints such as progression-free survival (PFS) to ensure that patients have speedy access to life-saving cancer medicines. However, the link between surrogate endpoints and overall survival (OS) is not well established in many cancers. OBJECTIVE: To characterize trends in endpoints used in pivotal trials leading to approval for US Food and Drug Administration (FDA)-approved solid tumor therapies and their efficacy from 1995 to 2021. METHODS: We reviewed the FDA Oncology (Cancer)/Hematologic Malignancies Approval Notifications webpage to extract data on median OS and PFS among solid tumor therapy approvals from 1995 to 2021. We summarized trends in percentage of trials reporting OS vs PFS, median OS and PFS, and trial designs. We conducted subgroup analyses for lung and breast cancer therapies. RESULTS: Median OS was reported more frequently until 2010 to 2012, when median PFS and OS were reported in 65.2% and 60.9% of trials, respectively. Between 1995 and 2021, there were no observable trends in median OS over time for solid tumor therapy approvals. Median PFS increased by 3.0 months over time. For lung cancer therapies, median OS increased by 6.8 months between the time periods of 1998-2000 and 2019-2021, whereas median PFS increased by 5.0 months between the time periods of 2007-2009 and 2019-2021. For breast cancer therapy, median OS slightly decreased over time, whereas median PFS has increased by 3.4 months since 1995. There has been a recent shift in use of single-arm trials leading to oncology drug approvals. CONCLUSIONS: There has been a transition from reporting OS to PFS, and median PFS has increased by 3 months while median OS has remained stable. The different trends in overall and progression-free survival highlights the challenge and importance of measuring the value of oncology drugs. DISCLOSURES: Dr Suh reports personal fees from Bayer US LLC.