A phase 2 trial of single‐agent bevacizumab given in an every‐3‐week schedule for patients with recurrent high‐grade gliomas

Abstract

BACKGROUND:The authors evaluated a 3-week schedule of bevacizumab in patients with recurrent high-grade glioma (HGG). METHODS: Patients received bevacizumab 15 mg/kg every 3 weeks and were evaluated every 6 weeks until tumor progression. Tissue correlates were used to quantify tumor content of vascular endothelial growth factor A (VEGFA) and vascular endothelial growth factor receptor-2 (VEGFR2). RESULTS: Of 61 patients who were treated (35 men and 26 women; median age, 52 years; age range, 21-78 years), 50 patients had glioblastoma multiforme (GBM), and 11 patients had anaplastic glioma (AG). The median number of previous chemotherapies was 2 (range, 1-5 previous chemotherapies), and 16 patients had received !3 previous chemotherapies. The median number of bevacizumab doses was 4 (range, 1-20 doses), and 45% of patients received >5 doses. The toxicities observed were primarily grade 1 and 2, and the most common were fatigue, hypertension, and headache. One grade 2 intratumoral bleed and 1 bowel perforation were reported. For patients with GBM, the 6-month progression-free survival rate was 25%, the median time to tumor progression was 10.8 weeks, and the median overall survival was 25.6 weeks. The best response included a partial response in 15 patients (24.5%) and stable disease in 31 patients (50.8%) patients; radiographic recurrence patterns included increased changes in fluid attenuation inversion recovery (24%) and multifocal recurrence (20%). The median survival after bevacizumab failure was 10 weeks. The ratio of tumor VEGFA/VEGFR2 was increased in patients aged >55 years; an increased VEGFA/VEGFR2 ratio was correlated nonsignificantly with decreased survival (P ¼ .052). CONCLUSIONS: An every-3-week schedule of bevacizumab had antitumor activity and was relatively nontoxic for patients with recurrent HGG. The predictive value of VEGFA/VEGFR2 in tumor will require validation in a larger patient cohort. Cancer 2010;116:5297-305.

Progression Pattern and Adverse Events with Bevacizumab in Glioblastoma

“…In fact, median os achieved in the B1L group was 13 months (95% ci: 10.0 to 26.0 months); in the B2L+ group, it was 7 months (95% ci: 3.2 to 8.0 months). Our results suggest that the use of bevacizumab in a second-line setting accords with the registration data for recurrent gbm [14][15][16][17][18][19][20][21][22] and should remain the current standard.…”

Therapeutic options in recurrent glioblastoma—An update

“…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].…”

“…Only one trial had a bevacizumab-free control arm with lomustine [54]. Most of these trials used bevacizumab at 10 mg/kg IV every 2 weeks except one study with 15 mg/kg IV every 3 weeks [87] and one study with 5 mg/kg IV every 3 weeks when combined with lomustine [58]. Toxicity of bevacizumab was mainly non-hematologic including hypertension, thrombembolic events, fatigue, and impaired wound healing.…”

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

“…35,36 Bevacizumab-Based Regimens in Patients With Recurrent Glioblastoma Multiple subsequent studies have been reported since provisional FDA approval, seeking to better define outcomes for bevacizumab, as well as to improve on them with alternative chemotherapy combinations. A prospective phase 2 study using every-3-week dosing of bevacizumab at a dose of 15 mg/kg in 61 patients with World Health Organization grade 3 or grade 4 glioma demonstrated no obvious differences in patient outcomes compared with contemporary studies using every-2-week dosing at 10 mg/kg, 37 thus allowing for flexibility in patient scheduling without clinical detriment. Several phase 2 trials of bevacizumab-based combinations have also been reported for recurrent glioblastoma (Table 1), 27,28,32, including bevacizumab with irinotecan, irinotecan plus cetuximab, irinotecan plus carboplatin, etoposide, fotemustine, sorafenib, temozolomide, erlotinib, and temsirolimus.…”