Progression-Free Survival 2 as a Potential Surrogate for Overall Survival in Glioblastoma: Insights From a Spanish Multicentric Cohort
Background In glioblastoma, first-line treatment can influence subsequent treatment lines. Therefore, progression-free survival 2 (PFS2), the time from initial randomization to progression on subsequent treatment or death, may better predict overall survival (OS) compared to PFS. However, this assoc...
| Autores: | , , , , , , , , , , , , , , , , , , , , , |
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| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2026 |
| País: | España |
| Institución: | Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau) |
| Repositorio: | r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau |
| OAI Identifier: | oai:dnet:r-iibsantpa_::9c1201d81a97c930f345ab77f76aec2c |
| Acceso en línea: | https://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=21461 |
| Access Level: | acceso abierto |
| Palabra clave: | clinical trial glioblastoma molecular targeted therapy progression-free survival surrogate endpoint |
| Sumario: | Background In glioblastoma, first-line treatment can influence subsequent treatment lines. Therefore, progression-free survival 2 (PFS2), the time from initial randomization to progression on subsequent treatment or death, may better predict overall survival (OS) compared to PFS. However, this association needs validation in glioblastoma, particularly with novel targeted agents in early clinical trials.Methods Medical records of glioblastoma patients from a multicentric Spanish cohort with genomic profiling treated between 2018 to 2023 were analyzed. Correlations between OS and PFS or PFS2 were calculated using an iterative multiple imputation approach and time-to-event endpoints with Kaplan-Meier methods.Results We analyzed 405 patients. Median OS, PFS, and PFS2 were 25.4, 8.7 and 16.4 months, respectively. Correlation between OS-PFS was 0.69 (95% CI, 0.62-0.75), whilst for OS-PFS2 it was 0.83 (95% CI, 0.78-0.87). In patients who received targeted therapy, OS-PFS correlation was 0.51 (95% CI, 0.02-0.81), whilst for OS-PFS2, it was 0.72 (95% CI, 0.30-0.91). For patients with ESCAT tier I-II molecular targets, OS-PFS correlation was 0.69 (95% CI, 0.26-0.89), weaker than OS-PFS2 (0.83 [95% CI, 0.29-0.97]). PFS2 also performed better than PFS in ESCAT III-IV patients (0.80 [95% CI, 0.75-0.85] vs. 0.69 [95% CI, 0.61-0.75]) and in those without targetable alterations (0.86 [95% CI, 0.74-0.92] vs. 0.68 [95% CI, 0.51-0.80]).Conclusions Progression-free survival 2 (PFS2) is a more robust surrogate for OS than PFS in glioblastoma, including patients receiving targeted therapies or without actionable targets. These findings support adoption of PFS2 as a candidate surrogate endpoint in glioblastoma, offering a balance between trial feasibility and meaningful survival outcomes. |
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