Heterogeneity of response to bevacizumab in multifocal and multicentric glioblastomas.

Abstract

2019 Background: Bevacizumab (BEV) is approved for treatment of recurrent glioblastoma (GBM). However, whether the subset of pts with multifocal (MF) or multicentric (MC) GBM respond favorably to BEV has not been described. Hypothesizing that MF/MC lesions may represent an initially more invasive and biologically heterogeneous phenotype in GBM which may exhibit varied responses to BEV, we examined their patterns of radiologic response and correlation with clinical outcome. Methods: Clinical and MRI data from pts with recurrent GBM who received BEV were reviewed to identify those with MC or MF disease who had adequate baseline and follow-up MRI. Enhancing and nonenhancing (FLAIR) disease were analyzed for response to BEV and categorized in each pt as homogeneous (similar changes in all lesions) or heterogeneous (varied across lesions) in response or progression. Progression-free survival (PFS) and overall survival (OS) were analyzed by the Kaplan Meier method and log rank test. Results: Of the 179 evaluable pts, 31 (17.3%) had multiple lesions (16 pts - MF, 15 pts - MC) prior to BEV treatment. Patients with MC/MF lesions had a significantly worse outcome than those with unifocal lesions in both PFS (Median 19 wks vs. 24.4 wks, p = 0.0124, HR 1.84, CI [1.14, 2.9]) and OS (Median 31 wks vs. 45.9 wks, p = 0.0011, HR 2.42, CI [1.42, 4.12]). Unlike previous reports of BEV response in recurrent GBM pts, MRI responders (homogenous or heterogeneous) among pts with MC/MF lesions did not have a better OS compared with nonresponders. In addition, no significant difference was seen in PFS or OS between patients with homogenous versus heterogeneous progression. There was no significant difference in median PFS (median 17.6 wks vs. 18.4 wks) or median OS (median 27.7 wks vs. 32.3 wks) between pts with MC versus MF GBM. Conclusions: The subset of GBM pts with MF/MC lesions had a worse outcome to BEV treatment compared with those with unifocal disease. Although a homogenous radiological response of all lesions to BEV was the commonest pattern on MRI, neither radiologic response nor pattern of radiologic progression correlated with improved PFS or OS. Our data also suggests that outcome of pts MC/MF GBM may need to be analyzed separately in studies with BEV containing regimens. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration IMEDEX Celgene, Lilly, MGI Pharma, Pfizer