Industry Sponsorship and Disease Site Focus in Therapeutic Radiopharmaceutical Clinical Trials Over the Past Decade.

Abstract

Purpose: Recent regulatory approvals of radiopharmaceutical therapies (RPTs) have brought increased attention to the modality. Knowledge of the RPT clinical trial landscape and its evolution will help practicing radiation oncologists prepare for the next generation of RPTs as they enter routine clinical practice.

Methods and materials: We queried ClinicalTrials.gov for therapeutic RPT clinical trials posted between 2014 and 2024. After excluding diagnostic and yttrium-90 [⁹⁰Y] microsphere therapeutic trials, we analyzed each posting. We characterized overall and temporal trends in primary disease site, trial phase, primary and secondary endpoints, industry sponsorship, and radioisotope/radioligand selection. Annual rates of change in trial postings and industry sponsorship were analyzed using Poisson and fractional logistic regression methods.

Results: The initial searches yielded 856 RPT clinical trials. After screening, 254 RPT trials were analyzed. The total number of annual trial postings demonstrated considerable growth during this period, with an approximate 13.0% year-over-year increase between 2014 and 2024. Prostate and neuroendocrine gastrointestinal cancers were the most commonly studied disease sites, accounting for 61.8% of trials. Efficacy and safety endpoints were the most common primary and secondary endpoints; however, notably, 24.4% of trials used a patient-reported quality of life indicator as a secondary endpoint. Trials involving lutetium-177 [¹⁷⁷Lu]-based agents accounted for 52.8% of therapeutic RPT trials over the past decade, with iodine-131 [¹³¹I] trials being the second most common at 15.7%. Specifically, ¹⁷⁷Lu-DOTATATE (26.0%) and ¹⁷⁷Lu-PSMA (22.4%) were the most commonly studied RPTs, followed by ¹³¹I (7.5%), radium-223 (²²³Ra, 6.7%), actinium-225 [²²⁵Ac]-PSMA (3.9%), and ¹³¹I-MIBG (3.9%). Nearly half (49.6%) of therapeutic RPT trials reported industry sponsorship, and the proportion of industry-sponsored trials increased consistently after 2017.

Conclusions: RPT trials demonstrated consistent growth over the past decade, largely driven by robust industry support, and have predominantly focused on targeted ¹⁷⁷Lu-based RPTs for the treatment of prostate adenocarcinoma and gastrointestinal neuroendocrine tumors.