Trends in eligibility criteria in solid tumor systemic therapy trials over time.

Abstract

e23018 Background: Friends of Cancer Research (FRIENDS) advocates for the broadening of eligibility criteria to ensure clinical trials are representative of real-world populations. Whether these recommendations have resulted in measurable changes in eligibility criteria over time remains unclear. We compared eligibility criteria in systemic therapy clinical trials for solid tumours conducted over a 10-year period. Methods: We identified randomized phase 2 and 3 clinical trial protocols evaluating systemic therapies for solid tumours published in 2012-2013 and 2022-2023 in the New England Journal of Medicine, Lancet, and Lancet Oncology. We focused on extraction of eligibility criteria on key recommendations from FRIENDS including HIV status, brain metastases, and organ dysfunction (e.g., myocardial infarction history). We compared eligibility criteria across the time points using Chi-square tests for categorical variables and Mann Whitney U tests for skewed continuous data. Results: We included 42 and 98 protocols from 2012-13 and 2022-23, respectively. Most protocols were phase III trials. Older protocols predominantly focused on breast, gastrointestinal, and skin cancers (33.3%; 11.9%; 14.3%), whereas more recent protocols more commonly evaluated gastrointestinal, genitourinary, and lung cancers (25.5%; 18.4%; 18.4%). Although targeted therapies were consistently examined across time, protocols shifted from a chemotherapy-dominant focus toward immunotherapy. Over time, there was a significant reduction in the proportion of studies excluding patients with brain metastases (71.4% in 2012-13 vs 33.0% in 2022-23). A higher proportion of 2022-23 protocols included patients with a history of myocardial infarction compared with 2012-23 protocols (26.2% vs 38.8%; p = 0.0001). Conversely, a higher proportion of recent protocols excluded patients with positive HIV status compared with older protocols (2012-13: not mentioned 64.3%; excluded 35.7%; 2022-23: not mentioned 21.4%; included with caveat 9.2%; excluded 69.4%). Conclusions: We observed significant differences in eligibility criteria over time. The increased inclusion of patients with brain metastases is encouraging; however, in other areas such as HIV status, ongoing work is needed to broaden criteria and ensure that trial populations are reflective of the real-world populations in which the drugs are likely to be used. These exclusions may compromise external validity and equity, highlighting the need for closer alignment with regulatory recommendations.