The earlier the better? Bevacizumab in the treatment of recurrent MGMT-non-methylated glioblastoma

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.