Plasma YKL-40 as a biomarker for bevacizumab efficacy in patients with newly diagnosed glioblastoma in the phase 3 randomized AVAglio trial.
Oncotarget
; 9(6): 6752-6762, 2018 Jan 23.
Article
em En
| MEDLINE
| ID: mdl-29467925
ABSTRACT
YKL-40 is a glycoprotein with pro-angiogenic functions. We hypothesized that patients with newly diagnosed glioblastoma and low baseline plasma YKL-40 levels derive greater benefit from first-line bevacizumab. Plasma samples were collected from 563 patients in the randomized, phase 3 AVAglio trial who received bevacizumab or placebo plus radiotherapy/temozolomide. Raw plasma YKL-40 concentrations were converted to age-corrected percentiles of normal healthy YKL-40 levels and divided into quartiles (Q). The impact of baseline plasma YKL-40 level on survival was investigated using Cox regression analyses. Patients with low baseline plasma YKL-40 (≤Q1) had an improved progression-free survival hazard ratio (HR) for bevacizumab versus placebo (0.37, 95% confidence interval [CI] 0.25-0.55) compared with high plasma YKL-40 (> Q1) (0.71, 95% CI 0.57-0.87). Overall survival HRs were comparable between the subgroups (≤ Q1 0.69, 95% CI 0.44-1.09; (> Q1 0.88, 95% CI 0.68-1.13). A trend for improved progression-free survival HR with low versus high YKL-40 was observed in proneural glioblastoma (0.41, 95% CI 0.13-1.28 vs 0.80, 95% CI 0.45-1.40, respectively), but not for proliferative/mesenchymal subtypes. Elevated plasma YKL-40 (> 90th percentile of normal) was an independent negative prognostic factor. In conclusion, the predictive value of baseline plasma YKL-40 level as a biomarker for bevacizumab efficacy in glioblastoma may be limited to patients with proneural tumors. Independent validation studies are required to confirm these results.
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1
Coleções:
01-internacional
Base de dados:
MEDLINE
Tipo de estudo:
Clinical_trials
/
Diagnostic_studies
/
Prognostic_studies
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article