Older Adult Participation in Early-Phase Lung Cancer Clinical Trials, 1998 to 2020

Despite advances, lung cancer treatment remains associated with substantial toxicity. Early-phase clinical trials inform the safety and efficacy of novel lung cancer treatments. Although older adults represent most patients with lung cancer, and they are underrepresented in phase 3 trials, age disparity in early-phase lung cancer trials is ill-defined.

We queried ClinicalTrials.gov to identify early-phase interventional clinical trials conducted in adults with lung cancer since database conception. We calculated the difference in age (DA) between the clinical trial populations and U.S. populations, using t test and one-sided analysis of variance to evaluate trial characteristics associated with DA.

We identified 141 clinical trials enrolling 7723 participants from 1998 to 2020. Early-phase lung cancer trial participants were, on average, 7.6 years younger than patients with lung cancer in the U.S. population (mean DA: -7.6 y, SD 4.2). Age disparities were magnified among clinical trials that were industry-sponsored (mean DA -8.5 versus -6.1, p = 0.001) and those limiting eligibility to Eastern Cooperative Oncology Group performance status less than or equal to 1 (mean DA -8.0 versus -6.0, p = 0.040). There was no association between the median age of trial participants and the proportion of patients with serious adverse events.

Older adults remain underrepresented in early-phase lung cancer clinical trials. With the rapid expansion of novel cancer therapies, focused efforts in the design of early-phase trials are warranted to reflect real-world populations. Otherwise, limitations in the generalizability of treatment safety and efficacy may increase in the future.