PMID- 38445445 OWN - NLM STAT- Publisher LR - 20240306 IS - 2095-3941 (Print) IS - 2095-3941 (Linking) DP - 2024 Mar 4 TI - Efficacy and safety of anlotinib combined with the STUPP regimen in patients with newly diagnosed glioblastoma: a multicenter, single-arm, phase II trial. LID - j.issn.2095-3941.2023.0373 [pii] LID - 10.20892/j.issn.2095-3941.2023.0373 [doi] AB - OBJECTIVE: Glioblastomas are highly vascularized malignant tumors. We determined the efficacy and safety of the anti-angiogenic multi-kinase inhibitor, anlotinib, for a newly diagnosed glioblastoma. METHODS: This multicenter, single-arm trial (NCT04119674) enrolled 33 treatment-naive patients with histologically proven glioblastomas between March 2019 and November 2020. Patients underwent treatment with the standard STUPP regimen [fractionated focal irradiation in daily fractions of 1.8-2 Gy given 5 d/w x 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) x 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/d. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS) and adverse events (AEs). RESULTS: Thirty-three patients received the planned treatment. The 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 therapy. Five patients discontinued treatment due to AEs. HEG1 (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 PFS. CONCLUSIONS: Anlotinib plus the STUPP regimen has promising anti-tumor activity against glioblastoma and manageable toxicity. HEG1 and RP1L1 alterations might be novel predictive biomarkers of the response to anlotinib. CI - Copyright (c) 2024 Cancer Biology & Medicine. FAU - Lai, Shuzhen AU - Lai S AD - Department of Radiation Oncology, The Second Affiliated Hospital of Soochow University, Suzhou 215000, China. AD - Department of Radiation Oncology, Yuebei People's Hospital Affiliated to the Medical College of Shantou University, Shaoguan 512026, China. FAU - Li, Peijing AU - Li P AD - Department of Radiation Oncology, The Cancer Hospital of the University of Chinese Academy of Sciences [Zhejiang Cancer Hospital Institute of Basic Medicine and Cancer (IBMC)], Chinese Academy of Sciences, Hangzhou 310022, China. FAU - Liu, Xiaohui AU - Liu X AD - Department of Radiation Oncology, The Second Clinical Medical College of Zhejiang Chinese Medical University, Hangzhou 311403, China. FAU - Liu, Guihong AU - Liu G AD - Department of Radiation Oncology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou 221004, China. FAU - Xie, Tieming AU - Xie T AD - Department of Radiology, The Cancer Hospital of the University of Chinese Academy of Sciences [Zhejiang Cancer Hospital Institute of Basic Medicine and Cancer (IBMC)], Chinese Academy of Sciences, Hangzhou 310022, China. FAU - Zhang, Xing AU - Zhang X AD - State Key Laboratory of Translational Medicine and Innovative Drug Development, Jiangsu Simcere Diagnostics Co., Ltd, Nanjing 210000, China. FAU - Wang, Xiaoxuan AU - Wang X AD - State Key Laboratory of Translational Medicine and Innovative Drug Development, Jiangsu Simcere Diagnostics Co., Ltd, Nanjing 210000, China. FAU - Huang, Jing AU - Huang J AD - Department of Radiation Oncology, The Affiliated Huai'an First People's Hospital of Nanjing Medical University, Huai'an 223399, China. FAU - Tang, Yiqiang AU - Tang Y AD - Department of Radiation Oncology, Jiangxi Cancer Hospital of Nanchang University, Nanchang 330029, China. FAU - Liu, Zhigang AU - Liu Z AD - Department of Radiotherapy, Dongguan Institute of Clinical Cancer Research, Dongguan Key Laboratory of Precision Diagnosis and Treatment for Tumors, Affiliated Dongguan Hospital, Southern Medical University, Dongguan 523059, China. AD - The Cancer Center, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai 519000, China. FAU - Shen, Guoping AU - Shen G AD - Department of Radiation Oncology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, China. FAU - Li, Chaoming AU - Li C AD - Department of Oncology, Maoming People's Hospital, Maoming 525000, China. FAU - Lu, Fangxiao AU - Lu F AD - Department of Radiology, The Cancer Hospital of the University of Chinese Academy of Sciences [Zhejiang Cancer Hospital Institute of Basic Medicine and Cancer (IBMC)], Chinese Academy of Sciences, Hangzhou 310022, China. FAU - Wang, Lei AU - Wang L AD - Department of Radiation Oncology, The Cancer Hospital of the University of Chinese Academy of Sciences [Zhejiang Cancer Hospital Institute of Basic Medicine and Cancer (IBMC)], Chinese Academy of Sciences, Hangzhou 310022, China. FAU - Jiang, Fagui AU - Jiang F AD - Department of Radiation Oncology, Kecheng District People's Hospital, Quzhou 324003, China. FAU - Sun, Caixing AU - Sun C AD - Department of Neurosurgery, The Cancer Hospital of the University of Chinese Academy of Sciences [Zhejiang Cancer Hospital Institute of Basic Medicine and Cancer (IBMC)], Chinese Academy of Sciences, Hangzhou 310022, China. FAU - Chen, Yuanyuan AU - Chen Y AUID- ORCID: 0000-0002-9655-7828 AD - Department of Radiation Oncology, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou 510060, China. AD - United Laboratory of Frontier Radiotherapy Technology of Sun Yat-sen University & Chinese Academy of Sciences Ion Medical Technology Co., Ltd, Guangzhou 510060, China. FAU - Chen, Ming AU - Chen M AUID- ORCID: 0000-0003-2570-0858 AD - Department of Radiation Oncology, The Second Affiliated Hospital of Soochow University, Suzhou 215000, China. AD - Department of Radiation Oncology, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou 510060, China. AD - United Laboratory of Frontier Radiotherapy Technology of Sun Yat-sen University & Chinese Academy of Sciences Ion Medical Technology Co., Ltd, Guangzhou 510060, China. LA - eng GR - 82272744/National Natural Science Foundation of China/ GR - 2022A1515010814/Natural Science Foundation of Guangdong Province/ GR - 2022008/Sun Yat-sen University Clinical Research 5010 Program/ PT - Journal Article DEP - 20240304 PL - China TA - Cancer Biol Med JT - Cancer biology & medicine JID - 101588850 SB - IM OTO - NOTNLM OT - Glioblastoma OT - anlotinib OT - anti-angiogenesis OT - multi-kinase inhibitor OT - progression-free survival OT - temozolomide COIS- No potential conflicts of interest are disclosed. EDAT- 2024/03/06 06:43 MHDA- 2024/03/06 06:43 CRDT- 2024/03/06 04:43 PHST- 2024/03/06 06:43 [medline] PHST- 2024/03/06 06:43 [pubmed] PHST- 2024/03/06 04:43 [entrez] AID - j.issn.2095-3941.2023.0373 [pii] AID - 10.20892/j.issn.2095-3941.2023.0373 [doi] PST - aheadofprint SO - Cancer Biol Med. 2024 Mar 4:j.issn.2095-3941.2023.0373. doi: 10.20892/j.issn.2095-3941.2023.0373.