Progression-Free Survival 2 as a Potential Surrogate for Overall Survival in Glioblastoma: Insights From a Spanish Multicentric Cohort


Por: Yaringaño, J, Mirallas, O, Navarro, V, Gómez-Puerto, D, Velilla, G, Vaz, MA, Gorria, T, Martínez-Monino, A, Hernández, A, Aguado, M, Di Muzio, A, Valbuena, DL, Ruiz-Pace, F, González, M, Martínez-García, M, Villacampa, G, Balaña, C, Carles, J, Dienstmann, R, Pineda, E, Sepúlveda, JM, Vieito, M

Publicada: 19 abr 2026
Resumen:
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.

Filiaciones:
Yaringaño, J:
 Vall dHebron Univ Hosp, Med Oncol Dept, Barcelona, Spain

Mirallas, O:
 Vall dHebron Univ Hosp, Med Oncol Dept, Barcelona, Spain

 Univ Texas MD Anderson Canc Ctr, Dept Invest Canc Therapeut, Div Canc Med, Houston, TX USA

Navarro, V:
 Vall Dhebron Inst Oncol, Stat Unit, Barcelona, Spain

Gómez-Puerto, D:
 Vall dHebron Univ Hosp, Med Oncol Dept, Barcelona, Spain

Velilla, G:
 Inst Invest Sanitaria Hosp 12 Octubre i 12, Neurol Dept, Madrid, Spain

Vaz, MA:
 Hosp Univ Ramon & Cajal, Med Oncol Dept, Madrid, Spain

Gorria, T:
 Hosp Clin Barcelona, Med Oncol Dept, Barcelona, Spain

Martínez-Monino, A:
 Hosp Mar, Res Inst, Med Oncol Dept, Barcelona, Spain

Hernández, A:
 Inst Catala Oncol Badalona, Badalona Appl Res Grp Oncol B ARGO Grp, Med Oncol, Badalona, Spain

Aguado, M:
 Hosp Santa Creu & Sant Pau, Med Oncol Dept, Barcelona, Spain

Di Muzio, A:
 IRCCS Humanitas Res Hosp, Med Oncol, Milan, Italy

Valbuena, DL:
 Vall dHebron Univ Hosp, Med Oncol Dept, Barcelona, Spain

Ruiz-Pace, F:
 Vall Dhebron Inst Oncol, Cellex Ctr, Oncol Data Sci ODysSey Grp, Barcelona, Spain

González, M:
 Vall dHebron Univ Hosp, Med Oncol Dept, Barcelona, Spain

Martínez-García, M:
 Hosp Mar, Res Inst, Med Oncol Dept, Barcelona, Spain

Villacampa, G:
 Vall Dhebron Inst Oncol, Stat Unit, Barcelona, Spain

Balaña, C:
 Germans Trias & Pujol Univ Hosp, ICO Inst Catala Oncol Badalona, Oncol Dept, Barcelona, Spain

Carles, J:
 Vall dHebron Univ Hosp, Med Oncol Dept, Barcelona, Spain

Dienstmann, R:
 Vall Dhebron Inst Oncol, Cellex Ctr, Oncol Data Sci ODysSey Grp, Barcelona, Spain

Pineda, E:
 Hosp Clin Barcelona, Med Oncol Dept, Barcelona, Spain

Sepúlveda, JM:
 Hosp 12 Octubre, Med Oncol Dept, Madrid, Spain

Vieito, M:
 Vall dHebron Univ Hosp, Med Oncol Dept, Barcelona, Spain
ISSN: 20457634





Cancer Medicine
Editorial
WILEY, 111 RIVER ST, HOBOKEN 07030-5774, NJ USA, Estados Unidos America
Tipo de documento: Article
Volumen: 15 Número: 4
Páginas:
WOS Id: 001743365500001
ID de PubMed: 42002922
imagen Green Submitted, gold

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