Efficacy and safety of anlotinib combined with the STUPP regimen in patients with newly diagnosed glioblastoma: a multicenter, single-arm, phase Ⅱ trial

作     者：Shuzhen Lai Peijing Li Xiaohui Liu Guihong Liu Tieming Xie Xing Zhang Xiaoxuan Wang Jing Huang Yiqiang Tang Zhigang Liu Guoping Shen Chaoming Li Fangxiao Lu Lei Wang Fagui Jiang Caixing Sun Yuanyuan Chen Ming Chen Shuzhen Lai;Peijing Li;Xiaohui Liu;Guihong Liu;Tieming Xie;Xing Zhang;Xiaoxuan Wang;Jing Huang;Yiqiang Tang;Zhigang Liu;Guoping Shen;Chaoming Li;Fangxiao Lu;Lei Wang;Fagui Jiang;Caixing Sun;Yuanyuan Chen;Ming Chen

作者机构：Department of Radiation OncologyThe Second Affiliated Hospital of Soochow UniversitySuzhou 215000China Department of Radiation OncologyYuebei People’s Hospital Affiliated to the Medical College of Shantou UniversityShaoguan 512026China Chinese Academy of SciencesHangzhou 310022China Department of Radiation OncologyThe Second Clinical Medical College of Zhejiang Chinese Medical UniversityHangzhou 311403China Department of Radiation OncologyThe Affiliated Hospital of Xuzhou Medical UniversityXuzhou 221004China Chinese Academy of SciencesHangzhou 310022China State Key Laboratory of Translational Medicine and Innovative Drug DevelopmentJiangsu Simcere Diagnostics Co.LtdNanjing 210000China Department of Radiation OncologyThe Affiliated Huai’an First People’s Hospital of Nanjing Medical UniversityHuai’an 223399China Department of Radiation OncologyJiangxi Cancer Hospital of Nanchang UniversityNanchang 330029China Department of RadiotherapyDongguan Institute of Clinical Cancer ResearchDongguan Key Laboratory of Precision Diagnosis and Treatment for TumorsAffiliated Dongguan HospitalSouthern Medical UniversityDongguan 523059China The Cancer CenterThe Fifth Affiliated Hospital of Sun Yat-Sen UniversityZhuhai 519000China Department of Radiation OncologyThe First Affiliated Hospital of Sun Yat-Sen UniversityGuangzhou 510080China Department of OncologyMaoming People’s HospitalMaoming 525000China Department of Radiation OncologyKecheng District People’s HospitalQuzhou 324003China Chinese Academy of SciencesHangzhou 310022China Department of Radiation OncologyState Key Laboratory of Oncology in South ChinaSun Yat-sen University Cancer CenterGuangzhou 510060China United Laboratory of Frontier Radiotherapy Technology of Sun Yat-sen University&Chinese Academy of Sciences Ion Medical Technology Co.LtdGuangzhou 510060China 

出 版 物：《Cancer Biology & Medicine》 (癌症生物学与医学（英文版）)

年 卷 期：2024年第21卷第5期

页      面：433-444页

核心收录：

学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

基　　金：supported by the National Natural Science Foundation of China(Grant No.82272744) Natural Science Foundation of Guangdong Province(Grant No.2022A1515010814) Sun Yat-sen University Clinical Research 5010 Program(Grant No.2022008) 

主　　题：Glioblastoma anti-angiogenesis multi-kinase inhibitor anlotinib temozolomide progression-free survival 

摘      要：Objective:Glioblastomas are highly vascularized malignant *** determined the efficacy and safety of the anti-angiogenic multi-kinase inhibitor,anlotinib,for a newly diagnosed ***:This multicenter,single-arm trial(NCT04119674)enrolled 33 treatment-naïve patients with histologically proven glioblastomas between March 2019 and November *** underwent treatment with the standard STUPP regimen[fractionated focal irradiation in daily fractions of 1.8-2 Gy given 5 d/w×6 w(total=54-60 Gy)]or radiotherapy plus continuous daily temozolomide(TMZ)(75 mg/m^(2)of body surface area/d,7 d/w from the first to the last day of radiotherapy),followed by 6 cycles of adjuvant TMZ(150-200 mg/m^(2)×5 d during each 28-d cycle)plus anlotinib(8 mg/d on d 1-14 of each 3-w cycle for 2 cycles during concomitant chemoradiotherapy,8 maximal cycles as adjuvant therapy,followed by maintenance at 8 mg/*** primary endpoint was progression-free survival(PFS).Secondary endpoints included overall survival(OS)and adverse events(AEs).Results:Thirty-three patients received the planned *** median PFS was 10.9 months(95%CI,9.9-18.7 months)and the 12-month PFS rate was 48.5%.The median OS was 17.4 months(95%CI,14.5-21.1 months)and the 12-month OS rate was 81.8%.The most common AEs included hypertriglyceridemia[58%(n=19)],hypoalbuminemia[46%(n=15)],and hypercholesterolemia[46%(n=15)]during concurrent chemoradiotherapy and leukopenia[73%(n=24)],hypertriglyceridemia[67%(n=22)],and neutropenia[52%(n=17)]during adjuvant *** patients discontinued treatment due to ***1(HR,5.6;95%CI,1.3-23.7;P=0.021)and RP1L1 alterations(HR,11.1;95%CI,2.2-57.2;P=0.004)were associated with a significantly shorter ***:Anlotinib plus the STUPP regimen has promising anti-tumor activity against glioblastoma and manageable ***1 and RP1L1 alterations might be novel predictive biomarkers of the response to anlotinib.