Christina Schaub1, Niklas Schäfer1,2, Frederic Mack1, Moritz Stuplich1, Sied Kebir1,2, Michael Niessen1, Theophilos Tzaridis1, Mohammed Banat3, Hartmut Vatter3, Andreas Waha4, Ulrich Herrlinger1, Martin Glas5,6,7. 1. Division of Clinical Neurooncology, Department of Neurology, University of Bonn Medical Center, Sigmund-Freud-Straße 25, 53105, Bonn, Germany. 2. Stem Cell Pathologies Group, Institute of Reconstructive Neurobiology, University of Bonn Medical Center, Sigmund-Freud-Straße 25, 53105, Bonn, Germany. 3. Department of Neurosurgery, University of Bonn Medical Center, Sigmund-Freud-Straße 25, 53105, Bonn, Germany. 4. Department of Neuropathology, University of Bonn Medical Center, Sigmund-Freud-Straße 25, 53105, Bonn, Germany. 5. 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. 6. 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. 7. Clinical Cooperation Unit Neurooncology, MediClin Robert Janker Klinik, Villenstraße 8, 53129, Bonn, Germany. martin.glas@ukb.uni-bonn.de.
Abstract
PURPOSE: 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). CONCLUSION: 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.
PURPOSE: 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). CONCLUSION: 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.
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