Evolving demographic representation and patient-reported outcomes in landmark antibody-drug conjugate trials supporting FDA approvals, 2015-2026.

Abstract

166 Background: Antibody-drug conjugates (ADCs) combine targeted delivery with potent cytotoxic payloads and are rapidly reshaping standard of care across solid and hematologic malignancies. As ADC use expand into earlier lines and broader populations, adequate representation of patients treated in real-world practice is increasingly important. ADCs are among the most expensive approved therapies, and their benefit-risk profiles may vary by age, comorbidity, and functional status. However, demographic representation and patient-reported outcome (PRO) reporting in pivotal ADC trials supporting regulatory approvals have not been systematically evaluated. Methods: We conducted a cross-sectional, trial-level analysis of pivotal studies supporting initial or major supplemental FDA approvals of ADCs or related antibody-toxin conjugates from January 2015 through June 16, 2026. Demographic characteristics, age-subgroup reporting, race and ethnicity, PRO inclusion, trial phase, disease category, and approval year were obtained from primary publications, trial reports, and FDA regulatory documents. Trials were categorized into early (2015-2019) and later (2020-2026) approval eras. Trial-level proportions were summarized using unweighted medians. Results: Thirty-two trials evaluating 16 agents and enrolling 15,542 participants were included. 20 trials were phase III (62.5%), 9 were phase II (28.1%), and 3 were phase I/II or Ib/II (9.4%). Twenty-two trials evaluated solid tumors (68.8%) and 10 evaluated hematologic malignancies (31.3%). Among 31 trials reporting a single overall median age, the median was 60 years (36-74); the median proportion of female participants was 52.4%. Twenty-three trials (71.9%) reported enrollment of patients aged ≥65 years, whereas only 9 (28.1%) provided full-trial data for patients aged ≥75 years. Race was available in 30 trials (93.8%) with median enrollment was 68.3% White, 2.1% Black, and 14.5% Asian. Median Hispanic representation was 6.0% among 17 trials reporting ethnicity. PROs were included in 19 trials (59.4%). Compared with 2015-2019, trials approved during 2020-2026 more frequently reported race data (96.0% vs 85.7%) and included PROs (64.0% vs 42.9%), whereas reporting of patients aged ≥75 years was less frequent (24.0% vs 42.9%). Conclusions: Despite increasing reliance on ADCs and improvements in accrual practices over time, landmark ADC trials continue to demonstrate limited representation of older adults and racial minority populations. As ADCs expand into earlier disease settings and broader populations, regulatory trials should prioritize representative enrollment, standardized age and race/ethnicity reporting, and prospective integration and publication of PROs to improve the equity, interpretability, and real-world generalizability of the evidence supporting their use.