Qun Chen

Supplementary Table S3. Summary of other trial results for recurrent glioblastoma.

Axial, sagittal and coronal gadolinium-enhanced and FLAIR MRI at pre-baseline (A-D). Three months later, MRI demonstrated progressive disease after anlotinib plus temozolomide (E-H).

A. An MR image revealed a hyperintense signal in the DWI sequence, indicating an acute ischemic stroke in the right ACA region (white arrows). B. CT angiography showed poor visualization of the distal ACA.

Supplementary figure 6. Wound dehiscence.

Axial, sagittal and coronal gadolinium-enhanced MRI at pre-baseline (A-C; yellow arrows), 6 months later demonstrating complete response after anlotinib plus temozolomide (E-G). Axial Fluid-Attenuated Inversion Recovery (FLAIR, D) image at pre-baseline, and no progression was observed during anlotinib plus temozolomide treatment after 6 months (H).

A-B. Kaplan-Meier plots of progression-free survival and overall survival (Full analysis set). The x-axes indicated times since enrollment.

Supplementary Table S2. Representativeness of Study Participants

A-B. Kaplan-Meier plots of progression-free survival and overall survival (Full analysis set). The x-axes indicated times since enrollment.

Supplementary Table S1. Patient Characteristics.

Purpose:Glioblastoma (GBM) is a highly vascularized tumor with few treatment options after disease recurrence. Here, we report the efficacy and safety of anlotinib hydrochloride plus temozolomide in patients with recurrent GBM.Patients and Methods:Patients with first definite postsurgical progression of histologically confirmed GBM preceded by standard radiotherapy and temozolomide chemotherapy were eligible for inclusion. All patients received temozolomide (150–200 mg/m2, orally, every day (QD) d1–5/4 wk) and anlotinib (10 mg, orally, QD, d1–14/3 wk) until disease progression or unacceptable toxicity. The primary endpoint was investigator-assessed 6-month progression-free survival (PFS) rate by the Response Assessment in Neuro-Oncology (RANO) criteria.Results:Twenty-one patients were enrolled between May 2020 and July 2021, with a median age of 55 (range 27–68) years old. According to the Response Assessment in Neuro-Oncology (RANO) criteria, tumor response occurred in 17 patients, of which 9 patients had a complete response, and the objective response rate was 81.0% [95% confidence interval (CI), 62.6–99.3]. The disease control rate was 95.2% (95% CI, 76.2–99.9), with three additional patients achieving a stable disease without tumor progression. The median PFS was 7.3 months (95% CI, 4.9–9.7), and the 6-month PFS rate was 61.9% (95% CI, 39.3–84.6). The median overall survival was 16.9 months (95% CI, 7.8–26.0). The most common adverse events were leukocytopenia (66.7%), thrombocytopenia (38.1%), and hypertriglyceridemia (38.1%). Five patients had nine grade 3 adverse events, with a 23.8% incidence rate. Two patients discontinued therapy due to ischemic stroke (grade 3) and wound dehiscence (grade 1), respectively. No grade 4 or treatment-related deaths occurred in this study.Conclusions:Anlotinib combined with temozolomide is efficacious and tolerated in patients with recurrent GBM.