Iannantuono Giovanni Maria, Floudas Charalampos S, Filetti Marco, Giovagnoli Tommaso, Sganga Stefano, Vitale Antonio, Chandran Elias, Lombardi Pasquale, Rosenfeld Roberto, Giudice Elena, Xue Elisabetta, Rapisarda Elvira, Troisi Paola, Apolo Andrea B, Karzai Fatima, Bria Emilio, Gulley James L, Daniele Gennaro
Phase 1 Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy.
Center for Immuno-Oncology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Eur J Cancer. 2025 Jul 25;225:115589. doi: 10.1016/j.ejca.2025.115589. Epub 2025 Jun 26.
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.
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).
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.
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.
功能状态低下的参与者通常被排除在癌症临床试验之外，这限制了试验结果的普遍性。在此，我们旨在调查导致抗癌药物获批的临床试验中的性能状态（PS）资格要求和入组特征。
我们对2009年至2023年期间美国食品药品监督管理局批准的非血液系统实体瘤关键临床试验进行了横断面研究。东部肿瘤协作组（ECOG）PS≥2的参与者被定义为功能状态低下（即PS差）。
我们确定了283项临床试验，共有158,510名参与者。四项（1.4%）研究未将PS作为资格标准。在其余279项试验中，72项（25.8%）允许PS差的参与者入组，在15年期间呈下降趋势（p = 0.01）。2009 - 2013年期间，纳入ECOG PS≥2参与者的研究比例为43.2%，2014 - 2018年为29.6%，2019 - 2023年为17.5%（p = 0.002）。值得注意的是，早期研究比3期临床试验更频繁地纳入PS差的参与者（40.8%对20.2%；p = 0.01）。最后，在15年期间，ECOG PS为0、1和2的参与者的中位数（四分位间距）比例分别为53.7%（38.7% - 65.7%）、45.1%（33.5% - 58.8%）和4.3%（1.8% - 7.9%）。
关键临床试验中纳入PS差的参与者比例有限，入组中位数百分比不到5%。申办者、机构审查委员会和研究者必须合作，拓宽PS资格标准，以获得更具代表性的试验人群。
