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Radiotherapy plus temozolomide with or without anlotinib in H3K27M-mutant diffuse midline glioma: A retrospective cohort study.
CNS Neuroscience & Therapeutics 2024 April
BACKGROUND: Besides the hallmark of H3K27M mutation, aberrant amplifications of receptor tyrosine kinases (RTKs) are commonly observed in diffuse midline glioma (DMG), a highly malignant brain tumor with dismal prognosis. Here, we intended to evaluate the efficacy and safety of a multitarget RTK inhibitor anlotinib in patients with H3K27M-DMG.
METHODS: A total of 40 newly diagnosed H3K27M-DMG patients including 15 with anlotinib and 25 without anlotinib treatment were retrospectively enrolled in this cohort. Progression-free survival (PFS), overall survival (OS), and toxicities were assessed and compared.
RESULTS: The median PFS and OS of all patients in this cohort were 8.5 months (95% CI, 6.5-11.3) and 15.5 months (95% CI, 12.6-17.1), respectively. According to the Response Assessment in Neuro-Oncology (RANO) criteria, the disease control rate in the anlotinib group [93.3%, 95% confidence interval (CI), 70.2-98.8] was significantly higher than those without anlotinib (64%, 95% CI: 40.5-79.8, p = 0.039). The median PFS of patients with and without anlotinib was 11.6 months (95% CI, 7.8-14.3) and 6.4 months (95% CI, 4.3-10.3), respectively. Both the median PFS and OS of DMG patients treated with anlotinib were longer than those without anlotinib in the infratentorial patients (PFS: 10.3 vs. 5.4 months, p = 0.006; OS: 16.6 vs. 8.7 months, p = 0.016). Multivariate analysis also indicated anlotinib (HR: 0.243, 95% CI: 0.066-0.896, p = 0.034) was an independent prognosticator for longer OS in the infratentorial subgroup. In addition, the adverse events of anlotinib administration were tolerable in the whole cohort.
CONCLUSIONS: This study first reported that anlotinib combined with Stupp regimen is a safe and feasible regimen for newly diagnosed patients with H3K27M-DMG. Further, anlotinib showed significant efficacy for H3K27M-DMG located in the infratentorial region.
METHODS: A total of 40 newly diagnosed H3K27M-DMG patients including 15 with anlotinib and 25 without anlotinib treatment were retrospectively enrolled in this cohort. Progression-free survival (PFS), overall survival (OS), and toxicities were assessed and compared.
RESULTS: The median PFS and OS of all patients in this cohort were 8.5 months (95% CI, 6.5-11.3) and 15.5 months (95% CI, 12.6-17.1), respectively. According to the Response Assessment in Neuro-Oncology (RANO) criteria, the disease control rate in the anlotinib group [93.3%, 95% confidence interval (CI), 70.2-98.8] was significantly higher than those without anlotinib (64%, 95% CI: 40.5-79.8, p = 0.039). The median PFS of patients with and without anlotinib was 11.6 months (95% CI, 7.8-14.3) and 6.4 months (95% CI, 4.3-10.3), respectively. Both the median PFS and OS of DMG patients treated with anlotinib were longer than those without anlotinib in the infratentorial patients (PFS: 10.3 vs. 5.4 months, p = 0.006; OS: 16.6 vs. 8.7 months, p = 0.016). Multivariate analysis also indicated anlotinib (HR: 0.243, 95% CI: 0.066-0.896, p = 0.034) was an independent prognosticator for longer OS in the infratentorial subgroup. In addition, the adverse events of anlotinib administration were tolerable in the whole cohort.
CONCLUSIONS: This study first reported that anlotinib combined with Stupp regimen is a safe and feasible regimen for newly diagnosed patients with H3K27M-DMG. Further, anlotinib showed significant efficacy for H3K27M-DMG located in the infratentorial region.
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