Liu Chao, Kuang Shuwen, Huang Tianxiang, Wu Jun, Zhang Longbo, Gong Xuan
Department of Oncology, Xiangya Hospital, Central South University, Changsha, China.
Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, China.
CNS Neurosci Ther. 2024 Apr;30(4):e14730. doi: 10.1111/cns.14730.
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.
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.
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.
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.
除了H3K27M突变这一特征外，受体酪氨酸激酶（RTK）的异常扩增在弥漫性中线胶质瘤（DMG）中普遍存在，DMG是一种预后极差的高度恶性脑肿瘤。在此，我们旨在评估多靶点RTK抑制剂安罗替尼对H3K27M-DMG患者的疗效和安全性。
本队列回顾性纳入了40例新诊断的H3K27M-DMG患者，其中15例接受安罗替尼治疗，25例未接受安罗替尼治疗。评估并比较无进展生存期（PFS）、总生存期（OS）和毒性。
该队列中所有患者的中位PFS和OS分别为8.5个月（95%CI，6.5-11.3）和15.5个月（95%CI，12.6-17.1）。根据神经肿瘤学疗效评估（RANO）标准，安罗替尼组的疾病控制率[93.3%，95%置信区间（CI），70.2-98.8]显著高于未使用安罗替尼的患者（64%，95%CI：40.5-79.8，p=0.039）。使用和未使用安罗替尼的患者中位PFS分别为11.6个月（95%CI，7.8-14.3）和6.4个月（95%CI，4.3-10.3）。幕下患者中，接受安罗替尼治疗的DMG患者的中位PFS和OS均长于未接受安罗替尼治疗的患者（PFS：10.3对5.4个月，p=0.006；OS：16.6对8.7个月，p=0.016）。多变量分析还表明，安罗替尼（HR：0.243，95%CI：0.066-0.896，p=0.034）是幕下亚组中OS延长的独立预后因素。此外，整个队列中安罗替尼给药的不良事件是可耐受的。
本研究首次报道，安罗替尼联合Stupp方案对新诊断的H3K27M-DMG患者是一种安全可行的方案。此外，安罗替尼对位于幕下区域的H3K27M-DMG显示出显著疗效。
