Randomized phase 2 study of carboplatin and bevacizumab in recurrent glioblastoma

Abstract

ACTRN12610000915055.

Therapeutic options in recurrent glioblastoma—An update

“…Toxicity of bevacizumab was mainly non-hematologic including hypertension, thrombembolic events, fatigue, and impaired wound healing. Overall response rates were similar in most trials with around one third of the patients mainly assessed by Macdonald criteria but also by RANO [54,90], while one trial only reports 6%, assessed by RANO criteria [84]. PFS-6 rates ranged from 18% to 42.6% and median OS from 6.5 to 9.2 months.…”

“…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.…”

“…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.…”

Bevacizumab and glioblastoma: Scientific review, newly reported updates, and ongoing controversies

“…32,[59][60][61][62][63][64][65][66][67][68] The randomized phase 2 GLARIUS trial compared bevacizumab, irinotecan, and radiotherapy versus standard temozolomide and radiation in patients with O 6 -methylguanine-methyltransferase (MGMT)-unmethylated, newly diagnosed glioblastoma. 59 This study found the combination of bevacizumab and irinotecan with radiotherapy to be more favorable than standard therapy, with the 6-month PFS rate reported at 79.5% versus 41.3%, and a mean PFS of 9.7 months versus 6 months, respectively.…”