Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 Jul 25:225:115589.
doi: 10.1016/j.ejca.2025.115589. Epub 2025 Jun 26.

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

Giovanni Maria Iannantuono  1 , Charalampos S Floudas  2 , Marco Filetti  1 , Tommaso Giovagnoli  1 , Stefano Sganga  3 , Antonio Vitale  3 , Elias Chandran  4 , Pasquale Lombardi  5 , Roberto Rosenfeld  6 , Elena Giudice  7 , Elisabetta Xue  2 , Elvira Rapisarda  8 , Paola Troisi  3 , Andrea B Apolo  4 , Fatima Karzai  4 , Emilio Bria  9 , James L Gulley  2 , Gennaro Daniele  10
Affiliations

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

Giovanni Maria Iannantuono et al. Eur J Cancer. .

Abstract

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.

Keywords: Clinical trial; Eligibility criteria; Performance status; Solid tumor.

PubMed Disclaimer

Conflict of interest statement

Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Emilio Bria: Grants or contracts from any entity: Astra Zeneca, Roche (Support to Institution). Consulting fees: MSD Oncology, Astra Zeneca, Pfizer, Roche, Takeda, Celltrion (Personal). Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: MSD Oncology, AstraZeneca, Pfizer, Roche, Takeda (Personal). Support for attending meetings and/or travel: MSD Oncology, Astra Zeneca (Personal). Participation on a Data Safety Monitoring Board or Advisory Board: MSD Oncology (Personal) Gennaro Daniele: Consulting fees: Bayer. Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: Astra Zeneca, Bayer, Gilead. Support for attending meetings and/or travel: Astra Zeneca, Roche The other authors declare that they have no conflict of interest.

Figures

Fig. 1.
Fig. 1.
Proportion of clinical trials enrolling poor-PS participants over the 15-year time interval.
Fig. 2.
Fig. 2.
Proportion of enrolled poor-PS participants over the 15-year time interval.
See this image and copyright information in PMC

References

    1. Stuart EA, Bradshaw CP, Leaf PJ. Assessing the generalizability of randomized trial results to target populations. Prev Sci 2015;16(3):475–85. 10.1007/s11121-014-0513-z. - DOI - PMC - PubMed
    1. Jin S, Pazdur R, Sridhara R. Re-evaluating eligibility criteria for oncology clinical trials: analysis of investigational new drug applications in 2015. J Clin Oncol 2017; 35(33):3745–52. 10.1200/JCO.2017.73.4186. - DOI - PMC - PubMed
    1. West HJ, Jin JO. JAMA oncology patient page. Performance status in patients with cancer. JAMA Oncol 2015;1(7):998. 10.1001/jamaoncol.2015.3113. - DOI - PubMed
    1. Karnofsky D, Abelmann W, Craver L, Burchenal J. The use of the nitrogen mustards in the palliative treatment of carcinoma. Part Ref Bronc Carcinoma Cancer 1948;1 (4):634–56. 10.1002/1097-0142(194811)1:4<634::AID-CNCR2820010410>3.0.CO;2-L. - DOI
    1. Scott JM, Stene G, Edvardsen E, Jones LW. Performance status in cancer: not broken, but time for an upgrade? J Clin Oncol 2020;38(25):2824–9. 10.1200/JCO.20.00721. - DOI - PMC - PubMed

Substances