DERIVATION OF MEANINGFUL WITHIN-PATIENT CHANGE (MWPC) THRESHOLDS OF THE EUROPEAN ORGANISATION FOR RESEARCH AND TREATMENT OF CANCER QUALITY OF LIFE QUESTIONNAIRE C30 (EORTC QLQ-C30) PHYSICAL FUNCTIONING (PF) SCORES FROM THE ASCENT-03 TRIAL
Author(s)
Yuanhui Zhang, PhD1, SAEID SHAHRAZ, MD, PhD2, Mira J. Patel, PhD2, Gary Leung, PhD2, Xin Li, PhD2, Rosemary Delaney, BSN, MPH2, Kevin Punie, MD3, Sara M. Tolaney, MD, MPH, FASCO4, Carlos Henrique Barrios, MD5, Andreas Schneeweiss, MD6, Javier Cortes, MD, PhD7.
1Gilead Sciences, Inc., Foster city, CA, USA, 2Gilead Sciences, Inc., Foster City, CA, USA, 3Oncology Center Antwerp, Ziekenhuis Aan de Stroom, Antwerp, Belgium, 4Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA, 5Latin American Cooperative Oncology Group (LACOG), Porto Alegre, Brazil, 6Heidelberg University Hospital and German Cancer Research Center, Heidelberg, Germany, 7International Breast Cancer Center, Pangaea Oncology, Quiron Group; IOB Madrid, Institute of Oncology, Hospital Beata María Ana; Hospital Universitario Torrejón, Ribera Group; Universidad Europea de Madrid, Faculty of Biomedical & Health Sciences; MEDSIR, Barcelona, Spain.
1Gilead Sciences, Inc., Foster city, CA, USA, 2Gilead Sciences, Inc., Foster City, CA, USA, 3Oncology Center Antwerp, Ziekenhuis Aan de Stroom, Antwerp, Belgium, 4Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA, 5Latin American Cooperative Oncology Group (LACOG), Porto Alegre, Brazil, 6Heidelberg University Hospital and German Cancer Research Center, Heidelberg, Germany, 7International Breast Cancer Center, Pangaea Oncology, Quiron Group; IOB Madrid, Institute of Oncology, Hospital Beata María Ana; Hospital Universitario Torrejón, Ribera Group; Universidad Europea de Madrid, Faculty of Biomedical & Health Sciences; MEDSIR, Barcelona, Spain.
OBJECTIVES: The EORTC QLQ-C30 PF subscale is a 5-item measure assessing a patient’s ability to perform daily physical activities, a key indicator of treatment impact on quality of life. We aimed to determine MWPC thresholds for EORTC QLQ-C30 PF scores in the first-line metastatic triple-negative breast cancer (mTNBC) population based on the randomized phase 3 ASCENT-03 trial, which included EORTC QLQ-C30 PF score at week 25 as a predefined key secondary endpoint.
METHODS: Analyses were conducted on the intent-to-treat population with baseline and ≥1 post-baseline PF assessment (through week 25; N=436). Participants completed EORTC QLQ-C30 at day 1 of each treatment cycle. Using pooled data from both treatment arms, anchor-based methods (ABMs; key anchors: Patient Global Impression of Severity [PGIS], Patient Global Impression of Change [PGIC]; supportive anchors: EORTC QLQ-C30 Items 29 and 30) were supplemented by distribution-based methods (DBMs). Spearman correlations (≥0.30) were used to confirm anchor validity. DBMs estimated MWPC using one-half standard deviation (1/2 SD) and standard error of measurement (SEM), calculated using test-retest reliability intra-class correlation coefficients (ICCs) from psychometrically and clinically stable PGIS and PGIC responses.
RESULTS: Of 436 participants, 293 had an assessment at week 25. Test-retest reliability ICC values were 0.87 based on PGIS response and 0.89 based on PGIC response. Correlations between PF changes through week 25 and anchors supported anchor adequacy (range: 0.39-0.50). Baseline DBM estimates for transformed PF scores were 9.76 (1/2 SD) and 7.00 (SEM). ABMs determined that between baseline and week 25, meaningful improvement was approximately +13.33 points, and worsening was -13.33 to -20.00 points, above the absolute value of ABM measures, corresponding to raw scores ≈0.4-0.6.
CONCLUSIONS: This analysis established MWPC thresholds of ±13.33 points in the first-line mTNBC population. This threshold will inform time-to-deterioration analyses and interpretation of PF outcomes in future clinical trials for this population.
METHODS: Analyses were conducted on the intent-to-treat population with baseline and ≥1 post-baseline PF assessment (through week 25; N=436). Participants completed EORTC QLQ-C30 at day 1 of each treatment cycle. Using pooled data from both treatment arms, anchor-based methods (ABMs; key anchors: Patient Global Impression of Severity [PGIS], Patient Global Impression of Change [PGIC]; supportive anchors: EORTC QLQ-C30 Items 29 and 30) were supplemented by distribution-based methods (DBMs). Spearman correlations (≥0.30) were used to confirm anchor validity. DBMs estimated MWPC using one-half standard deviation (1/2 SD) and standard error of measurement (SEM), calculated using test-retest reliability intra-class correlation coefficients (ICCs) from psychometrically and clinically stable PGIS and PGIC responses.
RESULTS: Of 436 participants, 293 had an assessment at week 25. Test-retest reliability ICC values were 0.87 based on PGIS response and 0.89 based on PGIC response. Correlations between PF changes through week 25 and anchors supported anchor adequacy (range: 0.39-0.50). Baseline DBM estimates for transformed PF scores were 9.76 (1/2 SD) and 7.00 (SEM). ABMs determined that between baseline and week 25, meaningful improvement was approximately +13.33 points, and worsening was -13.33 to -20.00 points, above the absolute value of ABM measures, corresponding to raw scores ≈0.4-0.6.
CONCLUSIONS: This analysis established MWPC thresholds of ±13.33 points in the first-line mTNBC population. This threshold will inform time-to-deterioration analyses and interpretation of PF outcomes in future clinical trials for this population.
Conference/Value in Health Info
2026-05, ISPOR 2026, Philadelphia, PA, USA
Value in Health, Volume 29, Issue S6
Code
P62
Topic
Patient-Centered Research
Topic Subcategory
Patient-reported Outcomes & Quality of Life Outcomes
Disease
SDC: Oncology