Association between Prior Malignancy Exclusion Criteria and Age Disparities in Cancer Clinical Trials

SIMPLE SUMMARY: Recent studies have shown that the incidence of age disparities in cancer clinical trials may be increasing over time. Excluding patients with prior malignancies is one such eligibility criterion through which elderly may inadvertently be excluded from clinical trial participation. While strict enrollment criteria may improve internal validity of studies, they can also negatively impact generalizability of results. As such, we sought to characterize the incidence of prior malignancy exclusion criteria in phase III cancer clinical trials and assess if this eligibility criterion may directly contribute to age disparities. These data support efforts to modernize eligibility criteria and inform best practices regarding acceptable versus unacceptable exclusionary timeframes for prior malignancy exclusion criteria. ABSTRACT: Prior malignancy exclusion criteria (PMEC) are often utilized in cancer clinical trials; however, the incidence of PMEC and the association of PMEC with trial participant age disparities remain poorly understood. This study aimed to identify age disparities in oncologic randomized clinical trials as a result of PMEC. Using a comprehensive collection of modern phase III cancer clinical trials obtained via ClinicalTrials.gov, we assessed the incidence and covariates associated with trials excluding patients with prior cancers within 5+ years from registration (PMEC-5). Using the National Cancer Institute Surveillance, Epidemiology, and End Results (SEER) database, we further sought to determine the correlation between PMEC-5 and age disparities. PMEC-5 were used in 41% of all trials, with higher PMEC-5 utilization among industry-supported trials as well as trials evaluating a targeted therapy. Comparing trial patient median ages with population-matched median ages by disease site and time-period, we assessed the association between PMEC-5 and age disparities among trial participants. PMEC-5 were independently associated with heightened age disparities, which further worsened with longer exclusionary timeframes. Together, PMEC likely contribute to age disparities, suggesting that eligibility criteria modernization through narrower PMEC timeframes may work toward reducing such disparities in cancer clinical trial enrollment.