Estimating meaningful change thresholds (MCTs) for selected scales from the European Organisation for Research and Treatment of Cancer (EORTC) questionnaires in the phase 3 SERENA-6 trial in patients with hormone receptor-positive/human epidermal growth factor receptor 2–negative advanced breast cancer (ABC).

409 Background: Interpretation of patient-reported outcome (PRO) data from oncology clinical trials requires that MCTs are defined for within-participant change and between-group differences. This study aimed to estimate MCTs for selected EORTC quality of life (QoL) 30-item core questionnaire (QLQ-C30) scales and breast cancer-specific module (QLQ-BR23) scales using data from the SERENA-6 study in patients with ABC switching first-line endocrine therapy at emergence of ESR1 mutations ahead of clinical or radiologic progression; patients switched to camizestrant or continued to receive aromatase inhibitor, with CDK4/6 inhibitor maintained. Methods: Pre-specified analyses were performed to define MCTs in EORTC-QLQ-C30 Global Health Status/Quality of Life (GHS/QoL), functional (physical, role, emotional, cognitive, social) and symptom (pain and fatigue) scores as well as EORTC-QLQ-BR23 arm and breast symptom scores using pooled, blinded patient data from baseline, weeks 12 and 28. Patient Global Impression of Severity, Patient Global Impression of Change, and EORTC-QLQ-C30 item 29 were used as anchors. Anchor adequacy was assessed using correlation coefficients, with values ≥0.371 considered adequate. Within-participant thresholds for both improvement and deterioration were derived through a triangulation process that utilized anchor- and distribution-based methods. Within-participant MCT estimates were additionally evaluated against the possible amount of change observable on each scale. For scales where no appropriate anchor was identified, distribution-based methods were used. Between-group thresholds were also estimated. Results: In total, 124, 121, and 82 participants had scores from evaluable forms at baseline, week 12, and week 28, respectively, for all scales. Anchor correlations were appropriate (≥0.371) for at least one anchor for all scales except for emotional functioning and arm symptoms, where anchor correlations were lower (< 0.371). Within-participant threshold for deterioration was estimated as –16.7 points for GHS/QoL, role, emotional, cognitive and social functioning, +16.7 points for pain and breast symptoms, +22.2 points for fatigue and arm symptoms, and –13.3 points for physical functioning. The between-group MCT ranged from 2.5 to 10.8 across the selected scales. Conclusions: MCTs were determined for the selected EORTC scales for use in the PRO endpoint definition and data interpretation in SERENA-6 and another study with a similar population. Using MCTs estimated from blinded study data provides context-specific thresholds that may accurately reflect a meaningful change in PROs for patients in the targeted study population. Clinical trial information: NCT04964934 .