Efficacy And Survival Analysis Of Apatinib In Patients With Advanced Nonsquamous Non-small Cell Lung Cancer After Failure Of First-line Treatment

Objective: The leading cause of cancer-related deaths in the world is lung cancer and most patients have metastases at the time of diagnosis.Many patients replace the standard first-line chemotherapy because of drug resistance,while the second or third line chemotherapy is inefficient.Angiogenesis plays an important role in maintaining tumor microenvironment,tumor growth and metastasis by means of providing oxygen and nutrients for proliferative cells.Apatinib,as a novel small molecule antiangiogenic drug,has demonstrated satisfactory anticancer activity across a broad range of malignancies.There are few clinical studies on the efficacy of apatinib in the treatment of advanced lung cancer at present.Therefore,this retrospective study was conducted to evaluate the safety and efficacy of apatinib in the treatment of advanced nonsquamous non-small cell lung cancer(NSCLC)after first-line treatment failure.Methods: From June 2015 to April 2017,128 patients with advanced non-squamous NSCLC who progressed after first-line treatment at Cancer Hospital of Tianjin Medical University were enrolled in this study.Patients were divided into apatinib monotherapy group(27),chemotherapy alone group(76)and apatinib combined with chemotherapy group(25).Following-up by telephone until September 2017,and sorting out clinical data.Statistical analysis relying on SPSS22.0 software.The chi-square test was used to compare the clinical characteristics and short-term curative effect.Nonparametric tests were used to compare adverse events.Kaplan-Meier method and Cox regression model were used for progression free survival(PFS)and overall survival(OS)analysis.Results: A total of 128 patients were enrolled in this study.The objective response rate(ORR)was 3.7%,2.6%,and 8.0% in apatinib monotherapy group,chemotherapy alone group and apatinib combined with chemotherapy group,respectively(c2= 1.238,P= 0.538),and the disease control rate(DCR)was 40.7%,44.7% and 68.0%,respectively(c2=4.888,P=0.087).The difference was not statistically significant.Comparing apatinib combined with chemotherapy to chemotherapy alone group,the median PFS---overall is 6.0 and 3 months,P<0.001;second line is 8.0 and 4.0 months,P=0.027;third line is 5.0 and 3.6 months,P=0.004 and OS---overall is 9.0 and 6.5 months,P=0.001;second line is 11.0 and 8.3 months,P=0.017;third line is 9.0 and 6.0 months,P=0.033,both showed significant statistical differences.Comparing apatinib monotherapy to chemotherapy alone group,the median PFS---overall is 3.0 and 3.7 months,P=0.381;second line is 4.6 and 4.0 months,P=0.221;third line is 3.0 and 3.6 months,P=0.803 and OS---overall is 6.0 and 6.5 months,P= 0.494;second line is 7.0 and 8.3 months,P=0.159;third line is 4.5 and 6.0 months,P=0.575,both without statistical differences.Univariate analysis showed that PS(P<0.001),pathological type(P=0.049)and treatment regimens(P=0.002)were correlated with PFS.PS(P<0.001),smoking history(P=0.040)and treatment regimens(P=0.007)were associated with OS.While gender,age,TNM stage,operation history and treatment stage were not associated with patients' prognosis.Multivariate analysis showed that pathological type was not the prognostic factor.Treatment regimens(P=0.001)and PS(P<0.001)were independent influencing factors of PFS.Smoking history(P=0.029),treatment regimen(P=0.002)and PS(P<0.001)were independent factors of OS.The incidence of adverse events in grade 3/4 were 18.5%,15.8% and 16.0%,respectively(P=0.947).Conclusion: Apatinib has a good security.After first-line treatment failure of advanced lung cancer,chemotherapy combined with apatinib in second or third line is beneficial in PFS and OS when compared with chemotherapy alone.But when making comparison between apatinib monotherapy and chemotherapy alone,there is no significant difference in PFS and OS.Patients who never smoke or has a better PS or use combination therapy have longer survival time.Patients who use apatinib combined with chemotherapy or has a better PS can get more benefit,in addition,those who never smoke have a better OS.