The Efficacy And Safety Of Apatinib In The Treatment Of Advanced Non-Small Cell Lung Cancer:a Retrospective Trial

Background and objective:The incidence rate of lung cancer is the main cause of cancer related morbidity and mortality worldwide,especially in developing countries.At present,the traditional combined chemotherapy and other treatment methods have reached the plateau stage of lung cancer treatment,and it is difficult to achieve a breakthrough in survival.The treatment of patients with advanced non-small cell lung cancer(NSCLC)has moved from the traditional chemotherapy era to the era of targeted therapy and immunotherapy.The formation of pathological neovascularization of tumor is involved in the process of the occurrence and development of various malignancies,and is related to malignant behaviors such as tumor growth,invasion and metastasis.In this process,multiple pathways are involved in tumor angiogenesis.Anti-angiogenic therapy targeting the vascular endothelial growth factor(VEGF)/VEGFR pathway is an important part of targeted therapy,which can inhibit tumor growth,invasion,metastasis and other malignant biological behaviors.Apatinib(YN968D1,Ai Tan)is a small molecule oral anti-VEGF/VEGFR drug independently developed in China.It mainly targets the VEGFR-2 molecule and inhibits the downstream signaling pathways.It has shown effective antiangiogenic activity in the treatment of breast cancer,colorectal cancer and other solid tumors and has obvious antitumor effect.In recent years,the application and research of apatinib in patients with advanced NSCLC are few and has not been accepted in the Clinical guidelines.The purpose of this study was to investigate the efficacy and safety of oral apatinib monotherapy as a second-line or above-second-line treatment for patients with advanced NSCLC,and to investigate the reasonable dosage of apatinib in the real world.Methods:This retrospective study collected clinical data of patients with advanced NSCLC treated with apatinib in Qilu Hospital of Shandong University during the period of June 1,2016 and March 31,2018.A total of 128 patients were enrolled,including 105 patients in the high-dose apatinib group(?500mg/d)and 23 patients in the low-dose apatinib group(<500mg/d).Telephone follow-up until February 1,2019.Solid tumor response evaluation criteria(RECIST)was used to evaluate patient outcomes,and common terminology criteria adverse events(CTCAE)version 4.0 was used to evaluate treatment-related adverse events(AEs).All statistical analyses were conducted by SPSS 23.0 statistical software.Chi square test was used to evaluate the clinical characteristics and short-term efficacy of the patients.Univariate and multivariate analyses were performed using Cox proportional risk model.Kaplan-meier curve was used to draw the survival curve of NSCLC patients,and then the correlation analysis of patients with progression-free survival(PFS)and overall survival(OS)was conducted.In this study,p<0.05 was considered statistically significant.Results:Among the 128 patients with advanced NSCLC treated with apatinib,the number of patients who achieved complete response(CR)was 0,15 patients achieved partial response(PR),and the number of patients who achieved stable disease(SD)was the most of 66,followed by 47 patients who had progression disease(PD).The overall objective response rate(ORR)was shown as 11.7%,and the total disease control rate(DCR)was 63.3%.The median PFS(mPFS)and median OS(mOS)were 4.2 and 7.7 months,respectively.The most common adverse reactions of apatinib were hypertension(HP)(48 cases),proteinuria(35 cases),and hand foot syndrome(HFS)(30 cases).Multivariate analysis showed that Eastern Cooperative Oncology Group Performance Status(ECOG PS)(HR 6.331,P<0.05),smoking history(HR 3.857,P<0.05),TNM stage(HR 1.731,P<0.05),and hypertension during treatment(HR 0.586,P<0.05)could be used as predictors of the efficacy of apatinib in the treatment of advanced NSCLC.In addition,there was no significant difference in efficacy or safety between the high-dose group(apatinib>500mg/d)and the low-dose group(apatinib<500mg/d).Conclusions:The short-term efficacy and survival benefits of apatinib in second-line or above treatment for patients with advanced NSCLC are satisfactory.The adverse reactions are low to moderate and the safety is controllable.The efficacy and safety of the low-dose apatinib group(<500mg/d)and the high-dose group(>500mg/d)were similar.