Apatinib Plus Temozolomide: An Effective Salvage Treatment for Recurrent Glioblastoma

Abstract

BackgroundTreatment for recurrent glioblastoma is poor, and there is a need for better therapies. Here we retrospectively assessed the efficacy and toxicity of temozolomide plus apatinib, an oral small-molecule tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor 2 in recurrent glioblastoma.Materials and MethodsA retrospective analysis of patients with recurrent glioblastoma who underwent apatinib plus temozolomide treatment was performed. Apatinib was given at 500 mg once daily. Temozolomide was administered at 200 mg/m2/d on days 1–5 or 50 mg/m2/d continuous daily according to whether they had experienced temozolomide maintenance treatment before. The main clinical data collected included tumor characteristics, status of MGMT promoter, and IDH mutation, number of relapse, response, survival, adverse reactions, and salvage therapies.ResultsFrom April 2016 to August 2019, thirty-one patients were identified. The objective response rate was 26.3%, and the disease control rate was 84.2%. The progression-free survival (PFS) at 6 months and overall survival (OS) at 12 months were 44.6 and 30.2%. The median PFS and OS were 4.9 and 8.2 months, respectively. Two patients achieved long PFS of 30.9 and 38.7+ months. The median survival time after progression of the patients with or without salvage bevacizumab was 5.1 versus 1.2 months. The most common grade 3 or 4 toxicities were hypertension (5.8%), decreased appetite (5.8%), and thrombocytopenia (4.3%), most of which were resolved after symptomatic treatment or dose reduction.ConclusionApatinib plus temozolomide is an effective salvage regimen with manageable toxicities for recurrent glioblastoma and could not reduce the sensitivity to bevacizumab.

Apatinib for recurrent/progressive glioblastoma multiforme: A salvage option

“…In this retrospective study, the ORR, the median PFS and OS were 52.6%, 5.1 months (95% CI, 4.5–5.7 months) and 10.4 months (95% CI, 6.3–14.5 months), respectively, which seemed to be better than the data of apatinib plus temozolomide for recurrent GBM in an observational study reported by Ge et al (2020) , with the ORR, the median PFS and the median OS were 26.3%, 4.9 months (95% CI, 2.8–7 months) and 8.2 months (95% CI, 6.9–9.5 months), respectively. Differing from previous studies mentioned above focusing on apatinib-based combination therapy, all patients in our study were treated with apatinib monotherapy, further suggesting the effectiveness of single-agent apatinib against recurrent/progressive GBM.…”

“…Currently, only a few case reports, retrospective and prospective studies with small sample sizes indicated that apatinib might be effective in the treatment of recurrent glioma ( Wang et al, 2017 ; Zhang et al, 2017 ; Ding et al, 2018 ; Wang et al, 2019 ; Ge et al, 2020 ; Hui et al, 2021 ; Zhu et al, 2022 ). Hence, we conducted this retrospective study to provide more clinical evidence of apatinib as a salvage therapy in recurrent/progressive GBM patients.…”

Combining apatinib and temozolomide for brainstem glioblastoma: a case report and review of literature

“…A prospective singlearm exploratory study including 15 recurrent glioblastoma patients thereafter yielded similar results, with a median PFS of 3.1 months and median OS of 8.7 months (17). These results were further confirmed in a retrospective analysis by Ge et al that showed a median PFS of 4.9 months and a median OS of 8.2 months (18). In addition, in a case report similar to ours, an adult with a brainstem anaplastic astrocytoma benefited from an initial treatment of combined radiotherapy, TMZ, and apatinib (500 mg/day) and had PFS of over 8 months (19).…”

Apatinib combined with temozolomide treatment for pseudoprogression in glioblastoma: A case report

“…[ 16 , 17 ] In a preclinical study, apatinib has the effect to suppress glioma cell proliferation and migration, and also to promote the anticancer effect of temozolomide. [ 18 ] Atinib treatment may be slightly toxic, resulting in anorexia (5.8%), hypertension (5.8%), thrombocytopenia (4.3%) and leucopenia (3.6%) in patients with grade III/ IV tumors. [ 18 ] Many of these toxic effects occur during early treatment and can be relieved by reducing the dose of apatinib and performing symptomatic management.…”

“…[ 18 ] Atinib treatment may be slightly toxic, resulting in anorexia (5.8%), hypertension (5.8%), thrombocytopenia (4.3%) and leucopenia (3.6%) in patients with grade III/ IV tumors. [ 18 ] Many of these toxic effects occur during early treatment and can be relieved by reducing the dose of apatinib and performing symptomatic management. Our results suggested that treatment with apatinib and temozolomide is effective and might be better than single temozolomide treatment, specifically for cases with MGMT non-methylation.…”