Plasma YKL-40 as a biomarker for bevacizumab efficacy in patients with newly diagnosed glioblastoma in the phase 3 randomized AVAglio trial

TY - JOUR

T1 - Plasma YKL-40 as a biomarker for bevacizumab efficacy in patients with newly diagnosed glioblastoma in the phase 3 randomized AVAglio trial

AU - Boisen, Mogens K.

AU - Holst, Camilla B.

AU - Consalvo, Nicola

AU - Chinot, Olivier L.

AU - Johansen, Julia S.

PY - 2018

Y1 - 2018

N2 - 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.

AB - 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.

KW - AVAglio

KW - Bevacizumab

KW - Glioblastoma

KW - Newly-diagnosed

KW - YKL-40

U2 - 10.18632/oncotarget.22886

DO - 10.18632/oncotarget.22886

M3 - Journal article

C2 - 29467925

AN - SCOPUS:85040944684

SN - 1949-2553

VL - 9

SP - 6752

EP - 6762

JO - Oncotarget

JF - Oncotarget

IS - 6

ER -