KEY TAKEAWAYS
- The phase 3 trial aimed to investigate the estimation of MCTs for selected EORTC scales in the TROPION-Breast01 trial of patients with advanced BC.
- Researchers noticed that MCTs provide valuable insights for interpreting PRO in BC trials and clinical practice.
Interpretation of clinical trial data is often hindered by the absence of defined Meaningful Change Thresholds (MCTs) for within-participant change and between-group differences in study endpoints.
Zhu Y and the team aimed to assess the estimated MCTs for selected European Organisation for Research and Treatment of Cancer (EORTC) scales utilized in the TROPION-Breast01 trial, focusing on patients with advanced breast cancer (BC).
They performed an inclusive analysis to define MCTs for selected EORTC scales in the TROPION-Breast01 trial. Pre-specified analyses encompassed various domains, including Global Health Status/Quality of Life (GHS/QoL), functioning (physical, role, emotional, cognitive, social), pain, fatigue, arm, and breast symptoms. Pooled blinded data from baseline, weeks 6, and 12 were utilized for this purpose.
Anchor appropriateness was evaluated via Spearman correlations, with values ≥0.371 deemed adequate. Both distribution and anchor-based methods were explored. Reliability coefficients, essential for distribution-based methods, were assessed for test-retest and internal consistency. Additionally, within-participant MCT estimates were compared with the potential observable change on each scale.
About 513 participants provided evaluable scores at baseline, with 384 participants across all time points. Anchor correlations were mostly low (<0.371), leading to limited consideration of anchor-based estimates. Thresholds were primarily estimated via distribution-based approaches, backed by adequate reliability for most scales.
Within-participant deterioration thresholds were determined: 11.1 for fatigue and arm symptoms, 13.3 for physical functioning, and 16.6 for GHS/QoL, functioning (role, emotional, cognitive, social), pain, and breast symptoms. GHS/QoL, physical functioning, and pain were utilized as trial secondary endpoints in time-to-deterioration analyses. The between-group difference MCT range spanned from 6.6 to 15.6.
The study concluded that deriving MCTs for selected EORTC scales significantly aided in interpreting Patient-Reported Outcome (PRO) endpoints within the trial. Furthermore, the potential utility of MCTs extends beyond clinical trials, offering valuable insights for routine care to comprehend the significance of longitudinal changes in patient outcomes.
The trial was sponsored by AstraZeneca.
Source: https://www.ispor.org/heor-resources/presentations-database/presentation/intl2024-3895/137346
Clinical Trial: https://clinicaltrials.gov/study/NCT05104866
Zhu Y, Bell J, Daskalopoulou C, et al. (2024). “Estimating Meaningful Change Thresholds (MCTs) for EORTC Scales in a Phase 3 Trial in Participants With Inoperable or Metastatic Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Breast Cancer.” Presented at ISPOR 2024.
