Efficacy of bevacizumab therapy for unresectable malignant glioma: A retrospective analysis

Abstract

Abstract. Bevacizumab (BEV), an inhibitor of vascular endothelial growth factor A, has been used for primary and recurrent malignant gliomas in Japan since June, 2013. Previous randomized controlled studies demonstrated that BEV prolonged the progression-free survival, but not the overall survival (OS) of patients with newly diagnosed glioblastoma. The aim of the present study was to elucidate the effect of BEV on the OS of patients with unresectable malignant gliomas. Of the 440 cases of malignant glioma initially treated in our institute between 2000 and 2015, 88 were not suitable for maximal resection due to patient age, physical condition, tumor location and extent, or the patient's wishes. Based on the biopsy results, the pathological diagnosis was glioblastoma, anaplastic astrocytoma and anaplastic oligodendroglioma in 60, 19 and 9 patients, respectively. Kaplan-Meier and log-rank analyses were performed to investigate the effect of BEV on OS. OS was longer in the BEV group (n=24) compared with that in the non-BEV group [n=64; median survival time (MST), 566 vs. 243 days, respectively; hazard ratio (HR)=0.413; 95% confidence interval (CI): 0.216-0.787; P=0.003]. In the 41 patients who received temozolomide (TMZ) and radiotherapy and the 31 patients with glioblastoma who received TMZ and radiotherapy, OS was longer in the BEV group compared with that in the non-BEV group (MST, 568 vs. 334 days, HR=0.404, 95% CI: 0.175-0.933, P=0.016; and MST, 566 vs. 160 days, HR=0.253, 95% CI: 0.099-0.646, P=0.001, respectively). In the Cox hazard model analysis of 41 patients who underwent TMZ-based chemoradiotherapy after biopsy, the use of BEV was the strongest independent beneficial factor associated with prolonged OS (HR=0.101; P=0.0002). Our retrospective survey suggested that BEV prolongs the OS of patients with unresectable malignant gliomas. However, these results must be verified by a well-designed prospective randomized controlled trial.

Bevacizumab in temozolomide refractory high-grade gliomas: single-centre experience and review of the literature

“…In contrast, significantly more patients within the intention-to-treat (ITT) population treated with BEV (299/465, 64.3%) completed all six cycles of TMZ, while only 165 of 446 in the placebo group did (37%, p < 0.0001), consistent with the shorter PFS in the placebo pus TMZ group. In contrast, Yonezawa and colleagues 34 reported a single-centre retrospective analysis of 88 cases with HGG, who over time received different primary adjuvant treatments, lomustine/procarbazine/vincristine from 2000 to 2006, TMZ from 2006 to 2013 and TMZ plus BEV from 2013 to 2016. Improvements in neurosurgical techniques were excluded as a confounder by choosing cases that received biopsies only.…”

“…A Cox proportional hazard model analysis led to BEV in addition with lower tumour grade and higher functional status as main predictor of prolonged survival. 34 In addition, a large retrospective study comprising 28.933 GB patients in the US prior TMZ approval, after TMZ approval and prior BEV approval for recurrent GB and after BEV approval showed an increasing OS over time due to administration of firstly TMZ concomitant with radiotherapy and adjuvant afterwards for newly diagnosed GB and then secondly due to the administration of BEV for recurrent GB. 35 …”

Update on Chemotherapeutic Approaches and Management of Bevacizumab Usage for Glioblastoma

“…Accordingly, real-world data from retrospective studies conducted by Japanese institutions appear promising in providing evidence of first-line BEV efficacy for patients with severe clinical conditions. Yonezawa et al [ 27 ] retrospectively analyzed newly diagnosed malignant glioma and reported that the use of BEV is an independent beneficial factor associated with prolonged OS in patients with unresectable GBM [BEV vs. non-BEV median OS: 566 vs. 160 days, HR 0.25 (0.10–0.65), p = 0.001]. We previously demonstrated that first-line BEV prevents deterioration during concurrent TMZ treatment and radiotherapy, and contributes to OS prolongation in patients with unresectable tumors (BEV vs. without BEV median OS: 17.4 vs. 9.8 months, p = 0.075) [ 28 ]; this highlights the advantages of first-line BEV for severe clinical conditions such as unresectable tumors and poor PS ( p = 0.017).…”

“…A possible reason for the failure of BEV to improve OS despite its prolongation of PFS in clinical trials is that BEV treatment may show changes in imaging findings that are not necessarily correlated with beneficial effects on tumor biology [ 30 ]. However, recent real-world data from Japanese institutes, in which BEV is available as a first-line treatment, indicate improved survival with selective administration of first-line BEV combined with TMZ for patients with severe clinical conditions such as unresectable cases or poor PS [ 27 , 28 , 29 , 31 ]. Nevertheless, the evidence level is not sufficiently high as these reports are institutional and retrospective studies, and BEV usage is institution-specific.…”

Injectable diblock copolypeptide hydrogel provides platform to deliver effective concentrations of paclitaxel to an intracranial xenograft model of glioblastoma

“…Despite maximal therapy including surgical resection, average survival is only 20 months [ 2 ]. Some patients are not candidates for surgery due to poor health, deep or bilateral location or proximity to eloquent structures [ 3 , 4 ]. Without cytoreductive surgery, the average survival is four months [ 2 ].…”