Analysis Of Non-Intervention Clinical Application Of Apatinib In The Treatment Of Advanced Malignant Tumors

Objectives Vascular endothelial growth factor(VEGF)and vascular endothelia growth factor recepter(VEGFR)are two important targets in signal transduction pathways of antiangiogenesis therapy targeting tumors.At present,the widespread use of some VEGFR inhibitors,such as ramucirumab,sorafenib and sunitinib,could improve the survival advantage of patients with certain advanced malignant tumors.This study aims to noninterventional observe the clinical efficacy and safety of apatinib,which targets VEGFR tyrosine kinases,and explore impact factors,in patients with common advanced malignant tumors.Methods In this study we collected patients with advanced malignant tumors who failed conventional second-line or more than second-line chemotherapy in two hospitals from August 2015 to October 2017.All the patients were given oral apatinib 425 mg once a day in 28-day cycle and adverse events were followed up and recorded.The observed indicators were progress free survival(PFS),objective response rate(ORR),and disease control rate(DCR).The baseline characteristics and adverse events were profiled for efficacy by Chi-square test,Kaplan-Meier and Log-Rank test.On this basis,Logistic regression model and COX proportional hazard model were used in multivariate regression to define the independent impact factors.Results From August 2015 to October 2017,one hundred sisty-five patients with advanced malignant tumors were enrolled in this study.Among them,one hundred fortyseven patients were evaluated for efficacy and(or)side effect,of which eighteen patients were excluded because they were not taken apatinib according to the medical order or they had no complete follow up data.The total median PFS was 3.29 months(95%CI: 2.999-3.581),the total ORR was 21.77%,and the total DCR was 70.75%.The most common drug-related adverse events included hypertension 57.14%(84/147),hand-foot syndrome(HFSR)52.38%(77/147),proteinuria 39.46%(58/147),fatigue 39.46%(58/147),abnormal liver function 23.13 %(34/147),no drug-related death.According to univariate analysis,PFS was significantly prolonged in patients with ECOG performance status(PS)0-1(4.29 m vs 2.68 m,P=0.000),and their ORR(28.2% vs 14.5%,P=0.044)and DCR(80.8% vs 59.4%,P=0.005)were better.PFS was significantly prolonged in patients with combination chemotherapy(4.32 m vs 2.86 m,P=0.000),and their ORR(40.0% vs 7.3%,P=0.000)and DCR(87.7% vs 57.3%,P=0.000)were better.PFS was significantly prolonged in the second-line treated patients(4.11 m vs 3.21 m,P=0.017),and their ORR(40.0% vs 17.1%,P=0.007)and DCR(86.7% vs 66.7%,P=0.032)were better.Analysis the drug-related sdverse events,PFS was significantly prolonged in patients with hypertension(4.29 m vs 2.32 m,P=0.000),and their ORR(29.8% vs 11.1%,P=0.007)was better.PFS was significantly prolonged in patients with HFSR(4.64 m vs 2.21 m,P=0.000),and their ORR(29.9% vs 12.9%,P=0.013)and DCR(81.8% vs 58.6%,P=0.002)were better.PFS was significantly prolonged in patients with fatigue(6.43 m vs 3.04 m,P=0.000),and their ORR(32.8% vs 14.6%,P=0.009)and DCR(82.8% vs 62.9%,P=0.010)were better.According to analysis of the COX proportional hazards model,ECOG performance status 0-1(P=0.000,HR=0.462),combined with chemotherapy(P=0.000,HR=0.462),hypertension(P=0.003,HR=0.550),HFSR(P=0.000,HR=0.470),and fatigue(P=0.000,HR=0.445)were the independent impact factors of PFS.According to analysis of the Logistic regression model,combined with chemotherapy was independent impact factor of better ORR(P=0.000,HR=0.139).Combined with chemotherapy(P=0.001,HR=0.234),ECOG 0-1(P=0.030,HR=0.030),HFSR(P=0.007,HR=0.007),and fatigue(P=0.030,HR=0.386)were independent impact factors of better DCR.Conclusions In this study,ECOG 0-1,combined with chemotherapy,hypertension,HFSR,and fatigue were the independent impact factors of PFS.Patients with combine with chemotherapy have a better ORR.Patients with combined with chemotherapy,ECOG 0-1,HFSR,and fatigue have a better DCR.Apatinib has good therapeutic efficacy in treating patients with some advanced malignant tumors.The side effects can be controlled and it is worth testing in large-scale clinical studies.