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.
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Ulrich Herrlinger has served as a consultant for Roche, Novocure, Mundipharma and Bristol-Myers-Squibb. He has received a scientific Grant from Roche and speakers honoraria from Roche, Medac and Riemser Pharma. Martin Glas has served as a consultant for Roche, Novartis, Mundipharma, sigma tau and UCB. He has received speakers honoraria from Roche, Medac and sigma tau, and a scientific Grant from Medac. Niklas Schäfer received honoraria from Roche. All other authors declare that they have no conflict of interest.
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All procedures performed in our study were in accordance with the ethical standards of the institutional research committee (local Ethic Committee) and with the 1964 Helsinki declaration and its later amendments. For this type of study, formal consent is not required.
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Ulrich Herrlinger and Martin Glas have contributed equally to this work.
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Schaub, C., Schäfer, N., Mack, F. et al. The earlier the better? Bevacizumab in the treatment of recurrent MGMT-non-methylated glioblastoma. J Cancer Res Clin Oncol 142, 1825–1829 (2016). https://doi.org/10.1007/s00432-016-2187-3
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DOI: https://doi.org/10.1007/s00432-016-2187-3