{"title":"安罗替尼联合 STUPP 方案对新诊断胶质母细胞瘤患者的疗效和安全性：一项多中心、单臂 II 期试验。","authors":"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","doi":"10.20892/j.issn.2095-3941.2023.0373","DOIUrl":null,"url":null,"abstract":"<p><strong>Objective: </strong>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.</p><p><strong>Methods: </strong>This multicenter, single-arm trial (NCT04119674) enrolled 33 treatment-naïve 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 × 6 w (total = 54-60 Gy)] or radiotherapy plus continuous daily temozolomide (TMZ) (75 mg/m<sup>2</sup> 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<sup>2</sup> × 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).</p><p><strong>Results: </strong>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% (<i>n</i> = 19)], hypoalbuminemia [46% (<i>n</i> = 15)], and hypercholesterolemia [46% (<i>n</i> = 15)] during concurrent chemoradiotherapy and leukopenia [73% (<i>n</i> = 24)], hypertriglyceridemia [67% (<i>n</i> = 22)], and neutropenia [52% (<i>n</i> = 17)] during adjuvant therapy. Five patients discontinued treatment due to AEs. <i>HEG1</i> (HR, 5.6; 95% CI, 1.3-23.7; <i>P</i> = 0.021) and <i>RP1L1</i> alterations (HR, 11.1; 95% CI, 2.2-57.2; <i>P</i> = 0.004) were associated with a significantly shorter PFS.</p><p><strong>Conclusions: </strong>Anlotinib plus the STUPP regimen has promising anti-tumor activity against glioblastoma and manageable toxicity. <i>HEG1</i> and <i>RP1L1</i> alterations might be novel predictive biomarkers of the response to anlotinib.</p>","PeriodicalId":9611,"journal":{"name":"Cancer Biology & Medicine","volume":" ","pages":""},"PeriodicalIF":5.6000,"publicationDate":"2024-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11131046/pdf/","citationCount":"0","resultStr":"{\"title\":\"Efficacy and safety of anlotinib combined with the STUPP regimen in patients with newly diagnosed glioblastoma: a multicenter, single-arm, phase II trial.\",\"authors\":\"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\",\"doi\":\"10.20892/j.issn.2095-3941.2023.0373\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Objective: </strong>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.</p><p><strong>Methods: </strong>This multicenter, single-arm trial (NCT04119674) enrolled 33 treatment-naïve 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 × 6 w (total = 54-60 Gy)] or radiotherapy plus continuous daily temozolomide (TMZ) (75 mg/m<sup>2</sup> 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<sup>2</sup> × 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).</p><p><strong>Results: </strong>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% (<i>n</i> = 19)], hypoalbuminemia [46% (<i>n</i> = 15)], and hypercholesterolemia [46% (<i>n</i> = 15)] during concurrent chemoradiotherapy and leukopenia [73% (<i>n</i> = 24)], hypertriglyceridemia [67% (<i>n</i> = 22)], and neutropenia [52% (<i>n</i> = 17)] during adjuvant therapy. Five patients discontinued treatment due to AEs. <i>HEG1</i> (HR, 5.6; 95% CI, 1.3-23.7; <i>P</i> = 0.021) and <i>RP1L1</i> alterations (HR, 11.1; 95% CI, 2.2-57.2; <i>P</i> = 0.004) were associated with a significantly shorter PFS.</p><p><strong>Conclusions: </strong>Anlotinib plus the STUPP regimen has promising anti-tumor activity against glioblastoma and manageable toxicity. <i>HEG1</i> and <i>RP1L1</i> alterations might be novel predictive biomarkers of the response to anlotinib.</p>\",\"PeriodicalId\":9611,\"journal\":{\"name\":\"Cancer Biology & Medicine\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":5.6000,\"publicationDate\":\"2024-03-04\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11131046/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Cancer Biology & Medicine\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.20892/j.issn.2095-3941.2023.0373\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"MEDICINE, RESEARCH & EXPERIMENTAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cancer Biology & Medicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.20892/j.issn.2095-3941.2023.0373","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}
Efficacy and safety of anlotinib combined with the STUPP regimen in patients with newly diagnosed glioblastoma: a multicenter, single-arm, phase II trial.
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-naïve 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 × 6 w (total = 54-60 Gy)] or radiotherapy plus continuous daily temozolomide (TMZ) (75 mg/m2 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/m2 × 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.
期刊介绍：
Cancer Biology & Medicine (ISSN 2095-3941) is a peer-reviewed open-access journal of Chinese Anti-cancer Association (CACA), which is the leading professional society of oncology in China. The journal quarterly provides innovative and significant information on biological basis of cancer, cancer microenvironment, translational cancer research, and all aspects of clinical cancer research. The journal also publishes significant perspectives on indigenous cancer types in China.
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