Racial, ethnic, sex, and age representation in clinical trials of radiopharmaceutical tumor therapy: a systematic review and meta-analysis.

BACKGROUND

Radiopharmaceutical therapy (RPT) is an emerging precision oncology approach. However, disparities in racial, ethnic, gender, and age representation in RPT cancer clinical trials may limit trial generalizability and equity. This study aims to quantify demographic disparities in RPT cancer clinical trials compared to US population data and examine trends and trial characteristics associated with these disparities.

METHODS

Systematic searches of PubMed, Web of Science (via MEDLINE), and ClinicalTrials.gov were conducted through November 2024. Population-based cancer data were obtained from the Surveillance, Epidemiology, and End Results (SEER) databases. All RPT clinical trials reporting age, race, ethnicity, or gender data and recruiting entirely in the US were included. Two reviewers independently extracted trial characteristics and demographic data. Enrollment incidence ratios (EIRs; < 1 indicates underrepresentation, > 1 indicates overrepresentation) were calculated for race, ethnicity, and gender, while median-age ratios (MRs; < 1 indicates younger trial participants compared to disease median diagnosis age) were used for age. Meta-analysis and meta-regression were performed to analyze disparities and trends over time.

RESULTS

Among 116 trials (5317 patients), reporting rates were 36.21% for race, 22.41% for ethnicity, 98.04% for gender, and 95.69% for median age. White participants were overrepresented (EIR: 1.04, 95% CI: 1.01-1.07), while Black (EIR: 0.32, 95% CI: 0.22-0.47), Asian/Pacific Islander (EIR: 0.55, 95% CI: 0.35-0.85), and Hispanic participants (EIR: 0.35, 95% CI: 0.24-0.51) were underrepresented. Female participants were also underrepresented (EIR: 0.83, 95% CI: 0.78-0.88). Trial participants had a lower median age compared to the SEER-reported median age at cancer diagnosis (MR: 0.86, 95% CI: 0.83-0.89). Meta-regression demonstrated modest improvements in gender, age, and racial/ethnic inclusion over time, particularly for Black and Hispanic participants, though disparities persist. Notably, industry-sponsored trials showed greater underrepresentation of Asian/Pacific Islander participants, and Hispanic inclusion was lower in trials studying cancers with higher 5-year survival rates and in two-arm trials compared to single-arm designs.

CONCLUSIONS

Significant demographic disparities persist in RPT trials, limiting the generalizability of findings. Inclusive trial designs, community engagement, and diversity mandates are essential to addressing these gaps and ensuring equitable access to RPT benefits.