Related Experiment Video
Updated: Sep 12, 2026
The Clinical Application of Tumor Treating Fields Therapy in Glioblastoma
Published on: April 16, 2019
A single-center retrospective study evaluating the efficacy of anlotinib plus temozolomide for recurrent glioma based
Yanyan Huang1, Wei Wei1, Yajing Xu1
1Glioma Medical Research Center and Department of Neurosurgery, The First Affiliated Hospital, Third Military Medical University (Army Medical University), Chongqing, China.
Background:
Recurrent gliomas are highly malignant intracranial tumors with poor overall outcomes and no consensus salvage treatment strategy. Vascular endothelial growth factor A (VEGF-A)/vascular endothelial growth factor receptor 2 (VEGFR-2)-dependent angiogenesis is a key driver of glioma progression. As an oral VEGFR-2 inhibitor with anti-tumor and anti-angiogenic activities, anlotinib may deliver clinical benefits for recurrent glioma, yet relevant clinical evidence remains limited. We herein aimed to evaluate the efficacy of anlotinib combined with temozolomide (TMZ) in patients with recurrent or residual glioma.
Methods:
This single-center retrospective cohort study enrolled patients with recurrent glioma treated with anlotinib combined with TMZ at The First Affiliated Hospital of Army Medical University between January 2020 and September 2025. Treatment was administered until disease progression or unmanageable toxicity. Progression-free survival from anlotinib plus metronomic TMZ treatment (PFS2) served as the primary endpoint; secondary endpoints included overall survival from anlotinib plus metronomic TMZ treatment (OS2), objective response rate (ORR), and disease control rate (DCR). Kaplan-Meier curves were applied for survival estimation, and Cox regression models were used to screen prognostic biomarkers.
Results:
A total of 39 patients were included [median age: 51 years; 61.54% World Health Organization (WHO) grade 4 glioma; 56.40% with methylated O6-methylguanine-DNA methyltransferase (MGMT) promoter]. The median PFS2 was 7.57 months [95% confidence interval (CI): 5.60-11.93], and median OS2 was 17.57 months (95% CI: 14.33-not estimable). Unmethylated MGMT promoter [hazard ratio (HR) =3.089, 95% CI: 1.074-8.886, P=0.04] and higher Ki-67 index (per 1% increment, HR =1.068, 95% CI: 1.036-1.101, P<0.001) independently predicted poorer post-recurrence survival. A Ki-67 cutoff of 7% differentiated WHO grade 2 from grade 3/4 gliomas, while the optimal cutoff of 25% predicted 6-month progression and 12-month mortality. Treatment-related adverse events were mostly mild, with few grade 3 toxicities and no treatment-associated deaths.
Conclusions:
Anlotinib combined with TMZ exhibited potential efficacy for recurrent gliomas, and the findings were merely hypothesis-generating. These exploratory results warrant validation in large randomized controlled trials to further confirm its clinical value.
