Analysis of eligibility and reporting standards for older patients with hormone receptor–positive, HER2-negative metastatic breast cancer (HR+ MBC) in pivotal phase III clinical trials, 2015-2025.

Abstract

e13087 Background: Despite the high burden of breast cancer among older adults, there remains underrepresentation of older patients in clinical trials and inconsistent reporting of data specific to older patients or geriatric-specific endpoints from pivotal trials. We sought to examine eligibility criteria, representation of older adults, reporting of age-stratified efficacy and safety, and inclusion of geriatric-specific variables from phase III randomized trials leading to FDA approval of new drugs or drug combinations for HR+ MBC over the past decade. Methods: We conducted a search to identify new FDA approvals for treatment of HR+ MBC between 2015 and 2025 and retrieved the corresponding phase III, registration trials. Data were extracted from publications of the primary trial results Extracted variables included the number and percentage of patients aged ≥65 years, which were compared with age-specific incidence estimates from SEER to calculate the Enrollment-to-Incidence Ratio (EIR). Additional trial characteristics extracted included the presence of explicit patient upper age limits, inclusion/exclusion criteria as reported in the trial protocol of primary manuscripts, use of geriatric assessments (any frailty index applied within the trial) and descriptive statistics were performed. Results: We identified 14 new FDA-approvals for HR+ MBC and identified the corresponding 14 pivotal trials (N = 7,848 patients) evaluating CDK4/6 inhibitors, PI3K pathway inhibitors, and other novel agents. Four trials (29%) imposed explicit upper age limits ( > 59, > 86, > 89, > 92 years). None of the trials (0%) performed geriatric assessment or frailty assessment. Nine trials explicitly reported the number of patients aged ≥65 years; among these trials (pooled N = 5,449), the sample-size–weighted mean proportion of patients aged ≥65 years was 31.7% (95% CI, 30.5%–32.9%). This is substantially below the 54.9% disease incidence in this age group (EIR: 0.58 [95% CI: 0.56-0.6]). In reporting progression-free and overall survival results, 42.8% (6/14) and 29% (4/14), stratified by age, respectively. None of the trials reported treatment dose modification or discontinuation rates, safety or quality of life stratified by age. Conclusions: Over the past decade, reports from the pivotal trials leading to FDA approvals for drugs to treat HR+ MBC inconsistently report information pertinent to treating older patients, including age-specific efficacy and safety information. None of the primary reports incorporated measures of frailty or geriatric-specific endpoints. These deficiencies limit the ability to translate efficacy and safety data to real-world older populations and highlight the need for more inclusive trial design, age-stratified reporting, and inclusion of variables specific to this population.