Performance status eligibility requirements and enrollment characteristics in cancer clinical trials leading to US Food and Drug Administration drugs approval (2009–2023)

Background

Participants with a low functional status are often excluded from cancer clinical trials, limiting the generalizability of their results. Here we aimed to investigate performance status (PS) eligibility requirements and enrollment characteristics in clinical trials leading to anticancer drug approvals.

Methods

We conducted a cross-sectional study on pivotal clinical trials for non-hematologic solid tumors leading to drug approvals by the US Food and Drug Administration from 2009 to 2023. Participants with an Eastern Cooperative Oncology Group (ECOG) PS ≥ 2 were defined as having low functional status (i.e., poor PS).

Results

We identified 283 clinical trials with 158,510 total participants. Four (1.4 %) studies did not use PS as an eligibility criterion. Of the remaining 279 trials, 72 (25.8 %) allowed the enrollment of poor-PS participants, with a negative trend over the 15-year interval (p = 0.01). The proportion of studies enrolling ECOG PS ≥ 2 participants was 43.2 % from 2009–2013, 29.6 % from 2014–2018, and 17.5 % from 2019–2023 (p = 0.002). Notably, early-phase studies included poor-PS participants more frequently than phase 3 clinical trials (40.8 % vs 20.2 %; p = 0.01). Finally, over the 15-year interval, the median (interquartile range) proportions of ECOG PS 0, 1, and 2 participants were 53.7 % (38.7 %–65.7 %), 45.1 % (33.5 %–58.8 %), and 4.3 % (1.8 %–7.9 %), respectively.

Conclusions

A limited fraction of pivotal clinical trials included participants with poor PS, with a median percentage enrollment of less than 5 %. Sponsors, institutional review boards, and investigators must collaborate to broaden PS eligibility criteria to achieve more representative trial populations.