Intermediate endpoints as surrogates for long-term outcomes in breast cancer adjuvant chemotherapy trials
Importance and Objective: Several definitions of efficacy endpoints have been proposed for clinical trials in early breast cancer (EBC). Invasive disease-free survival (IDFS) and other endpoints have been used as surrogates for overall survival (OS) in adjuvant trials. The aim was to evaluate these...
| Autores: | , , , , , , , , , , , , , , , , , |
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| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2025 |
| País: | España |
| Institución: | INCLIVA |
| Repositorio: | r-INCLIVA. Repositorio Institucional de Producción Científica de INCLIVA |
| OAI Identifier: | oai:incliva.fundanetsuite.com:p20269 |
| Acceso en línea: | https://incliva.portalinvestigacion.com/publicaciones/20269 |
| Access Level: | acceso abierto |
| Palabra clave: | breast cancer early-stage surrogate endpoint adjuvant chemotherapy |
| Sumario: | Importance and Objective: Several definitions of efficacy endpoints have been proposed for clinical trials in early breast cancer (EBC). Invasive disease-free survival (IDFS) and other endpoints have been used as surrogates for overall survival (OS) in adjuvant trials. The aim was to evaluate these endpoints in a comparative way in a large cohort of patients to assess whether they are appropriate surrogates for OS. Participants and Design: Individual patient data from 8 phase III randomized adjuvant chemotherapy (CT) trials for EBC were analyzed. Trial-level surrogacy analyses were conducted using weighted least squares regression to assess the association between treatment effects on surrogates at different time points-IDFS and other defined endpoints (by STEEP v2.0)-and OS. Correlation between the log hazard ratio (HR) of the endpoints and OS were quantified using R-2 values. Preplanned subgroup analyses by tumor subtype were also performed. Results: Results censoring at 5 years and at longer follow-up (median: 9.6 years) were similar. HR of IDFS and invasive BC-free survival (IBCFS) at 5 years showed a R-2 > 0.7 relative to HR of OS. All other surrogates revealed correlations with R-2 > 0.5. For patients with hormone receptor-positive/HER2-negative intermediate/high-risk tumors, correlation showed higher R-2 for IDFS (R-2 = 0.89; 95% confidence interval [CI] = [0.80-0.98]) and IBCFS (R-2 = 0.84; 95% CI = [0.71-0.97]) than distant-recurrence endpoints, while for those with triple negative tumors the highest correlation was seen with distant disease-free survival (R-2 = 0.86; 95% CI = [0.75-0.98]). Conclusions and Relevance: Although all studied endpoints are appropriate surrogates for OS when evaluating CT-based adjuvant interventions, investigators should consider the BC subtype to select the primary endpoint. Trial registration number: ClinTrials.gov: GEICAM/9805: NCT00121992; GEICAM/9906: NCT00129922; GEICAM/2003-02: NCT00129389; GEICAM/2003-10: NCT00129935; CIBOMA/2004-01_GEICAM/2003-11: NCT00130533; BCIRG 001: NCT00688740; BCIRG 005: NCT00312208 and BCIRG 006: NCT00021255. |
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