The earlier the better? Bevacizumab in the treatment of recurrent MGMT-non-methylated glioblastoma.
OBJECTIVE
The adequate second-line therapy of patients with glioblastoma (GBM) is a matter of ongoing debate. This particularly applies to patients with a non-methylated MGMT promotor who are known to have a poor response to alkylating chemotherapy. In some countries, antiangiogenic therapy with BEV is applied as second-line therapy, and in others nitrosourea therapy is second-line choice. It is an open question whether the delay of BEV to third-line therapy has a negative impact on survival.


METHODS
A total of 61 adult patients (median age 56.9 years) with MGMT-non-methylated relapsed GBM treated with BEV (n = 45) or nitrosourea (n = 16) as second-line therapy were analyzed retrospectively and compared regarding progression-free survival (PFS) and overall survival (OS).


RESULTS
Patients treated with second-line BEV had longer median PFS (107 days, 95 % CI 80.7-133.2 days) than patients with second-line nitrosourea (52 days, 95 % CI 36.3-67.7 days, P = 0.011, logrank test). However, there was no significant difference in overall survival (BEV median 170 days, 95 % CI 87.2-252.8 days; nitrosourea median 256 days, 95 % CI 159.9-352.0 days, P = 0.468). PFS was similar after BEV third-line therapy (median 117 days, 95 % CI 23.6-210.4 days) as compared to second-line BEV therapy (median 107 days, 95 % CI 80.7-133.3 days, P = 0.584).


CONCLUSIONS
Our findings suggest that early treatment with BEV in patients with MGMT-non-methylated relapsed GBM is associated with a better PFS, but not with superior OS, possibly implicating that the early, i.e., second-line, use of BEV is not mandatory and BEV treatment may safely be delayed to third-line therapy in this subgroup of patients.
Division of Clinical Neurooncology, Department of Neurology, University of Bonn Medical Center, Sigmund-Freud-Straße 25, 53105, Bonn, Germany.
Christina
C
Schaub
Division of Clinical Neurooncology, Department of Neurology, University of Bonn Medical Center, Sigmund-Freud-Straße 25, 53105, Bonn, Germany.|Stem Cell Pathologies Group, Institute of Reconstructive Neurobiology, University of Bonn Medical Center, Sigmund-Freud-Straße 25, 53105, Bonn, Germany.
Niklas
N
Schäfer
Division of Clinical Neurooncology, Department of Neurology, University of Bonn Medical Center, Sigmund-Freud-Straße 25, 53105, Bonn, Germany.
Frederic
F
Mack
Division of Clinical Neurooncology, Department of Neurology, University of Bonn Medical Center, Sigmund-Freud-Straße 25, 53105, Bonn, Germany.
Moritz
M
Stuplich
Division of Clinical Neurooncology, Department of Neurology, University of Bonn Medical Center, Sigmund-Freud-Straße 25, 53105, Bonn, Germany.|Stem Cell Pathologies Group, Institute of Reconstructive Neurobiology, University of Bonn Medical Center, Sigmund-Freud-Straße 25, 53105, Bonn, Germany.
Sied
S
Kebir
Division of Clinical Neurooncology, Department of Neurology, University of Bonn Medical Center, Sigmund-Freud-Straße 25, 53105, Bonn, Germany.
Michael
M
Niessen
Division of Clinical Neurooncology, Department of Neurology, University of Bonn Medical Center, Sigmund-Freud-Straße 25, 53105, Bonn, Germany.
Theophilos
T
Tzaridis
Department of Neurosurgery, University of Bonn Medical Center, Sigmund-Freud-Straße 25, 53105, Bonn, Germany.
Mohammed
M
Banat
Department of Neurosurgery, University of Bonn Medical Center, Sigmund-Freud-Straße 25, 53105, Bonn, Germany.
Hartmut
H
Vatter
Department of Neuropathology, University of Bonn Medical Center, Sigmund-Freud-Straße 25, 53105, Bonn, Germany.
Andreas
A
Waha
Division of Clinical Neurooncology, Department of Neurology, University of Bonn Medical Center, Sigmund-Freud-Straße 25, 53105, Bonn, Germany.
Ulrich
U
Herrlinger
Division of Clinical Neurooncology, Department of Neurology, University of Bonn Medical Center, Sigmund-Freud-Straße 25, 53105, Bonn, Germany. martin.glas@ukb.uni-bonn.de.|Stem Cell Pathologies Group, Institute of Reconstructive Neurobiology, University of Bonn Medical Center, Sigmund-Freud-Straße 25, 53105, Bonn, Germany. martin.glas@ukb.uni-bonn.de.|Clinical Cooperation Unit Neurooncology, MediClin Robert Janker Klinik, Villenstraße 8, 53129, Bonn, Germany. martin.glas@ukb.uni-bonn.de.
Martin
M
Glas
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000068258:Bevacizumab / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D005260:Female; D005909:Glioblastoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local
D000970:Antineoplastic Agents; D000068258:Bevacizumab
Bevacizumab; Nitrosourea; Recurrent MGMT-non-methylated glioblastoma; Survival outcome