Bevacizumab Alone and in Combination With Irinotecan in Recurrent Glioblastoma

Abstract

Bevacizumab, alone or in combination with irinotecan, was well tolerated and active in recurrent glioblastoma.

Therapeutic options in recurrent glioblastoma—An update

“…aflibercept, sunitinib, vandetanib or nintedanib failed to give an efficacy signal. Cediranib, a pan-tyrosine kinase inhibitor of VEGFR achieved similar response rates and PFS-6-data as did bevacizumab in phase II [85,86,106]. The subsequent phase III trial of cediranib showed comparable but not better efficacy than lomustine.…”

“…A detailed listing of all trials with these agents, mostly conducted as single arm studies, would be beyond the scope of this review. Carboplatin (CABARET trial) and irinotecan (BRAIN trial) have been evaluated in randomized phase II trials as add-ons to bevacizumab (Table 3) [84,85]. Both trials were negative showing no difference in outcome but additional toxicity in the treatment arms with carboplatin and irinotecan.…”

“…Table 3 summarizes trials with single-arm monotherapy, randomized trials and single arm combination containing bevacizumab. Bevacizumab was approved in 2009 for the treatment of recurrent glioblastoma by the FDA and in several other countries based on the results of 2 uncontrolled phase II trials with overall response rates of about one third of the patients and with PFS-6 rates of 42.6 and 29% [85,86]. In Europe, approval was refused because of the lack of a bevacizumab-free control arm.…”

“…In Europe, approval was refused because of the lack of a bevacizumab-free control arm. There are 9 phase II trials with a bevacizumab monotherapy arm, 3 of them single-arm studies [86][87][88], 5 trials compared bevacizumab with bevacizumab plus another agent, such as irinotecan [85], carboplatin [84], the histone-deacetylase inhibitor vorinostat [89], the multikinase inhibitor dasatinib [90] or lomustine [58]. Only one trial had a bevacizumab-free control arm with lomustine [54].…”

“…PFS-6 rates ranged from 18% to 42.6% and median OS from 6.5 to 9.2 months. In the randomized trials adding another experimental agent to bevacizumab (irinotecan, carboplatin, vorinostat or dasatinib) versus bevacizumab alone, both arms showed comparable efficacy leading to the conclusion of poor efficacy of the experimental agent without valid evidence regarding the single agent activity of bevacizumab [84,85,89,90]. The BELOB trial comprising a bevacizumab-free control arm showed comparable single agent activity of bevacizumab versus lomustine.…”