Lb-05phase Iii Trial Exploring the Combination of Bevacizumab and Lomustine in Patients With First Recurrence of a Glioblastoma: The Eortc 26101 Trial

Therapeutic options in recurrent glioblastoma—An update

“…The BELOB trial comprising a bevacizumab-free control arm showed comparable single agent activity of bevacizumab versus lomustine. However, as already discussed, median OS of the combination of bevacizumab and lomustine was superior to single agent activity in this phase II trial in contrast to the EORTC 26101 phase III trial showing no difference in OS of the combination versus lomustine alone [54,56].…”

“…The future role of bevacizumab is uncertain since the EORTC 26101 trial failed to demonstrate superiority for OS of lomustine plus bevacizumab over lomustine alone [56]. Many single-arm trials are difficult to interpret because of the lack of a controlled and randomized design and heterogeneous cohorts.…”

“…Again, hematological toxicity was relevant with 22% of the patients discontinuing fotemustine due to grade 3 or 4 myelotoxicity. The promising efficacy signal of the combination of nitrosoureas with bevacizumab of phase II trials was not confirmed in the EORTC 26101 phase III trial comparing lomustine plus bevacizumab with lomustine alone in patients with recurrent glioblastoma which did not report a difference in OS (8.6 versus 9.1 months), although prolonged PFS (1.5 versus 4.2 months) was confirmed [56].…”

“…Nitrosoureas [52][53][54][55][56] and 1 trial with carmustine where data for patients treated with carmustine (n=29) were not separately reported but summarized in a common "control" arm with 27 patients receiving TMZ [57]. All but 3 trials were conducted at the first recurrence after TMZ-based standard radiochemotherapy.…”

“…No efficacy signal beyond the data for bevacizumab monotherapy was seen except for lomustine at phase II with negative results in the comparative phase III trial (EORTC 26101) [54,56]; in addition, some of the combination trials reported increased toxicity.…”