Abstract
BACKGROUND: Bevacizumab, a monoclonal antibody targeting vascular
endothelial growth factor A (VEGF-A) has shown activity in the treatment of
recurrent malignant glioma. Predictive markers and prognostic models are required
in order to individualize treatment for grade 3 glioma patients. The
primary endpoint of this study was to identify predictive biomarkers associated
with response to bevacizumab therapy. The secondary endpoint was to
identify prognostic factors associated with progression-free survival (PFS)
and overall survival (OS). METHODS: A total of 62 consecutive, recurrent
grade 3 glioma patients were administered bevacizumab and irinotecan
between December 2005 andNovember 2014 according to a previously published
clinical protocol.Awide range of clinical, histopathological and molecular
factors were screened for significant correlation (p , 0.05) with response
and survival endpoints using logistic and Cox regression, respectively.
Potentially predictive biomarkers were subjected to multivariate analysis.
The landmark method was employed for analysis of survival by response.
RESULTS: Twenty-two of 57 evaluable patients (38.6 %) demonstrated a response
at the time of their best response MRI (RANO criteria). Responders
had significantly prolonged OS (p ¼ 0.007) and trended toward longer PFS
(p ¼ 0.067) as compared to non-responders (OS: 12.4 vs 4.3 months, PFS:
5.6 vs 3.2 months). A favorable WHO performance status (PS) and absence
of necrosis were significantly more common in responders than nonresponders.
Multivariate analysis also identified a poor PS as the only prognostic
factor for PFS, while an unfavorable PS and immunohistochemical p53 accumulation
were prognostic of reducedOS.CONCLUSIONS:Apoor baseline
PS and the presence of necrosis were negatively associated with response to
bevacizumab. An unfavorable PS and p53 positivity are prognostic of worse
outcome in this patient population.
endothelial growth factor A (VEGF-A) has shown activity in the treatment of
recurrent malignant glioma. Predictive markers and prognostic models are required
in order to individualize treatment for grade 3 glioma patients. The
primary endpoint of this study was to identify predictive biomarkers associated
with response to bevacizumab therapy. The secondary endpoint was to
identify prognostic factors associated with progression-free survival (PFS)
and overall survival (OS). METHODS: A total of 62 consecutive, recurrent
grade 3 glioma patients were administered bevacizumab and irinotecan
between December 2005 andNovember 2014 according to a previously published
clinical protocol.Awide range of clinical, histopathological and molecular
factors were screened for significant correlation (p , 0.05) with response
and survival endpoints using logistic and Cox regression, respectively.
Potentially predictive biomarkers were subjected to multivariate analysis.
The landmark method was employed for analysis of survival by response.
RESULTS: Twenty-two of 57 evaluable patients (38.6 %) demonstrated a response
at the time of their best response MRI (RANO criteria). Responders
had significantly prolonged OS (p ¼ 0.007) and trended toward longer PFS
(p ¼ 0.067) as compared to non-responders (OS: 12.4 vs 4.3 months, PFS:
5.6 vs 3.2 months). A favorable WHO performance status (PS) and absence
of necrosis were significantly more common in responders than nonresponders.
Multivariate analysis also identified a poor PS as the only prognostic
factor for PFS, while an unfavorable PS and immunohistochemical p53 accumulation
were prognostic of reducedOS.CONCLUSIONS:Apoor baseline
PS and the presence of necrosis were negatively associated with response to
bevacizumab. An unfavorable PS and p53 positivity are prognostic of worse
outcome in this patient population.
| Original language | English |
|---|---|
| Publication date | 2015 |
| DOIs | |
| Publication status | Published - 2015 |