| BackgroundSmall cell lung cancer(SCLC)accounts for about 15%of all lung cancers.Most patients are extensive stage in diagnosis,with a very poor outcome.The standard first-line treatment of extensive SCLC is still etoposide combined with cisplatin(EP)for over the last 40 years,and subsequent treatments are very limited once disease progressed.Apatinib is a small molecule inhibitor of vascular endothelial growth factor receptor-2 tyrosine kinase,which can block the transmission of VEGF/VEGFR-2 signaling pathway.Apatinib has shown efficacy against several cancers including NSCLC,but its efficacy in SCLC is still unclear.Apatinib combined with etoposide capsules has demonstrated efficacy in ovarian cancer.Therefore,we conducted this prospective,single-arm,phase Ⅱ clinical trial to evaluate the efficacy and safety of apatinib combined with etoposide capsules in third-line and above for the treatment of advanced SCLC.ObjectiveTo evaluate whether apatinib combined with etoposide capsules can prolong the progression-free survival(PFS,progression-free survival),overall survival time(OS,overall survival)and objective response rate(ORR)of advanced SCLC patients.MethodsThis study is a multi-center,single arm,phase Ⅱ study conducted in 11 medical institutions in China.All enrolled patients received apatinib(250mg/qd,po)and etoposide capsules(50mg/d.po,for 21 days,drug withdrawal for 7 days.28 days per cycle)until PD(disease progression),death or intolerable toxicity.SPSS25.0 software was used for statistical analysis,Kaplan-Meier method was used to draw survival curve,Log-rank test was used for single factor analysis,and COX proportional hazards regression model was used for multivariate analysis.P<0.05 was considered statistically significant.This research was funded by the National Natural Science Foundation of China(Project Number:81272600)and received the ethics approval from the Ethics Committee of the Cancer Hospital Affiliated to Zhengzhou University on November 29,2017.All patients signed informed consent.ResultsFrom January 2018 to February 2020.a total of 56 patients with advanced SCLC who failed second-line and above treatment were included.53 patients were included in the ITT set.Among them.patients with ECOG score of 0-1 accounted for 92.5%(49/53).and patients with score of 2 accounted for 7.5%(4/53).As of March 5.2020.50 patients(94.34%)had disease progression and 39 patients(73.58%)died.The best efficacy evaluations were 0 CR.11 PR.37 SD.5 PD,the ORR was 20.75%(11/53)and DCR was 86.54%(48/53).The median follow-up time was 9.8 months(4.9-19.2 months).The median progression-free survival time was 3.3 months(95%CI:2.554-4.046),and the median overall survival was 5.0 months(95%CI:3.403-6.597).The 6-month and 12-month OS rate were 41.51%(22/53.95%CI:8.9-1 1.8).1 1.32%(6/53,95%CI:1 1.5-17.2)respectively.The results of multivariate analysis show that the best efficacy evaluation and brain metastasis are independent influencing factors for PFS in advanced SCLC patients(P<0.05),while the best efficacy evaluation and brain metastasis are also important factors for OS(P<0.05).The main common Ⅰ/Ⅱgrade adverse reactions are:leukopenia(30.2%),fatigue(28.3%),anemia(24.5%),nausea(24.5%),proteinuria(18.9%),vomiting(18.9%),hand-foot syndrome(17%),thrombocytopenia(17%),hypertension(15.1%),and so on.No grade Ⅲ/Ⅳ adverse events were reported.ConclusionsApatinib combined with etoposide capsules can prolong the PFS and OS for extensive SCLC patients in third-line and above treatment setting compared with history data.This regimen is well tolerated and the no grade III/IV adverse events were reported.Apatinib combined with etoposide capsules may be an optional choice for extensive SCLC in third-line or above treatment.The best therapeutic effect of patients during the treatment with this regimen is a predictor of patients’progression-free survival time and overall survival time. |
PDF Full Text Request