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
Green Submitted, gold
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