Efficacy of Anlotinib in Treating Progressive Glioblastoma: Insights From a Single-Center Study

Abstract

BACKGROUND Glioblastoma (GBM) is the most common and aggressive malignant tumor in the central nervous system, with limited therapeutic options and poor prognosis. Anlotinib, a novel multi-targeted tyrosine kinase inhibitor, has shown promise in treating various malignancies. This study systematically analyzed the treatment outcomes of 10 typical patients with progressive GBM in our institution who were treated with anlotinib. MATERIAL AND METHODS Ten progressive GBM patients treated with anlotinib between 2020 and 2022 were included. Tumor progression was assessed using modified Response Assessment in Neuro-Oncology (mRANO) criteria. Disease progression was evaluated via conventional MRI and physical examinations. Patient condition was measured using the Karnofsky performance status (KPS) scale and the European Organization for Research and Treatment Core Quality of Life Questionnaire (EORTC QLQ-C30). Median progression-free survival (PFS) and overall survival (OS) were calculated from anlotinib initiation. Adverse effects were graded using CTCAE 5.0. RESULTS According to the mRANO criteria, 3 patients had a complete response, 3 had a partial response, 1 had stable disease, and 3 had progressive disease, resulting in a 70% disease control rate and a 60% objective response rate. Median PFS was 5.42 months, and median OS was 6.30 months. KPS scores significantly improved after treatment (P<0.05), and QLQ-C30 scores were higher in 11 of 15 items (P<0.05). No grade 3 or 4 adverse events were observed. CONCLUSIONS Through small-sample real-world research, anlotinib, either as monotherapy or in combination with temozolomide, demonstrated promising therapeutic effects in patients with progressive GBM, suggesting its potential as a targeted treatment option.

Figure 1. Summary of treatment process

Swimmer plot of 10 patients with GBM at admission and treated with anlotinib after the tumor has progressed. The plot was sorted by overall survival. The line chart began after the resection of each patient’s lesion. The blue line represents the process of TMZ treatment, while the orange line depicts the procedure of concurrent anlotinib and TMZ use. The gray line shows patients had a second tumor progression. Between those 3 periods of treatment, we used blue and green string to distinguish them. Rhombus symbolized the patients’ death. Some of the patients have passed away (7 of 10), and some of them is living (3 of 10).

Figure 2. Changes of KPS scores across different conditions

(A) Line chart of Karnofsky performance status score. The line chart shows mean KPS score of 10 patients. A comparison of pre- and postoperative status shows the status has improved after tumor resection. Among patients who received anlotinib treatment, an improvement in KPS score was commonly observed, suggesting a potential beneficial effect on functional status during therapy. (B) An improvement in KPS was observed following the administration of anlotinib. Table shows the distinction between tumor progression and anlotinib used. According to the result of the 2-tailed t test, we could easily identify anlotinib has significantly improve the KPS score (P<0.05).

Figure 3. Main neuroimaging of illustrative case 1 during treatment process

Illustrative case 1 shows anlotinib treatment efficacy. In Figure 3, 8 separate figures show preoperative, postoperative, tumor progression, and anlotinib efficacy in MRI (contrast-enhanced T1 sequence). Figure A and B show the patient’s preoperative condition. Postoperative MRI in Figures C and D demonstrates gross total resection of the tumor. Subsequent tumor progression was identified based on MRI findings and clinical symptoms (E, F). After anlotinib treatment, neuroimaging shows enhancement in MRI was relieved (G, H), and the symptoms caused by tumor progression were alleviated.

Figure 4. Main neuroimaging of illustrative case 2 during treatment process

Neuroimaging of the treatment process in illustrative case 2. There were 8 separated figures showing preoperative (A, B), postoperative (C, D), tumor progression (E, F), and anlotinib efficiency (G, H) in MRI (contrast-enhanced T1 sequence). Preoperatively, A and B show the tumor located in the callosum. Because of its deep location, we used stereotactic biopsy to detect tumor grade and determine further treatment measures. In neuroimaging after biopsy, we could easily notice that the lesion has been partial resected (C, D). After months of TMZ treatment, the tumor has progressed and enhancement was detected on MRI (E, F). With anlotinib use, neuroimaging showed relieved tumor progression and the symptoms caused by tumor progression were alleviated (G, H).

Figure 5. Main neuroimaging of illustrative case 3 during treatment process

The treatment process of illustrative case 3. Preoperative (A–C), postoperative (D–F), tumor progression (G–I), and anlotinib used (J–L) in neuroimaging (MRI, contrast-enhanced T1 sequence). In postoperative neuroimaging (A–C), the lesion is easily observed in the temporo-parietal occipital lobe, with significant enhancement in contrast-enhanced T1 sequence. Postoperatively, MRI confirmed gross total resection of the tumor (D–F). However, follow-up MRI performed several months after completion of the Stupp protocol revealed radiographic evidence of tumor progression (G–I). After anlotinib use, MRI showed enhancement was relieved, as were the symptoms caused by tumor progression (J–L).