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 multicente...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/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/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.展开更多
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).
文摘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/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/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.
