Safety And Efficacy Of Apatinib In Recurrent Epithelial Ovarian Cancer

ObjectiveTo evaluate the safety and efficacy of apatinib in recurrent epithelial ovarian cancer.MethodsFrom August 2016 to December 2020,patients who received apatinib combined with or without chemotherapy from Qilu Hospital of Shandong University were collected.All patients were diagnosed with recurrent epithelial ovarian cancer.The initial dose pf apatinib was 250mg/d or 500mg/d depending on the statue of patients.Apatinib treatment was stopped until disease progression or an intolerant adverse event occurs after dose adjustment or drug interruption.The adverse reactions during apatinib treatment were recorded to evaluate drug safety.The median progression-free survival(PFS),objective response rate(ORR)and disease control rate(DCR)were used to evaluate the efficacy.Correlation analysis between different chemotherapy groups was evaluated by Chi-square test and t test.Log-rank test was used to analyze the prognostic factors.ResultsA total of 32 patients were enrolled.The median duration of follow-up at the time of data analysis was 17.0 months(range 3.7-37.7)and mean administration time was 4.7 cycles.The overall median PFS was 4.6 months,The overall median PFS was 4.6 months in the enrolled 32 patients,and who received apatinib combined with chemotherapy had a median PFS of 4.9 months,which had no statistically significant(P=0.372).The median PFS was 5.0 months for those who had received≤5 previous chemotherapy regimens,compared with 3.6 months(P=0.126).The median PFS of patients with platinum-resistant ovarian cancer was 4.2 months,and there was no statistically significant compared with patients with platinum-sensitive ovarian cancer(P=0.655).We also compared median PFS of patients whether received previous bevacizumab treatment and found there was no statistical difference(4.0vs.4.6,P=0.925).The overall ORR was 37.5%and DCR was 84.4%,respectively.ORR of patients received apatinib monotherapy was 14.3%and that combination chemotherapy group was 63.6%(P=0.027).DCR was 85.7%and 81.8%in monotherapy group and combination chemotherapy group(P=0.782).Log-rank test was performed and patients with hand-foot syndrome was found to had better PFS(6.3 months vs.3.0 months,P=0.039),which we considered hand-foot syndrome as a predictive factor of PFS.The most common adverse reactions of apatinib included hypertension(53.1%),hand-foot syndrome(46.9%),proteinuria(40.6%).The most common hematologic toxicity was neutropenia(34.4%).The most common grade 3/4 adverse events were mucositis oral(9.4%)and neutropenia(9.4%).Patients were divided into 2 groups based on different initial doses.The low-dose group included 13 patients received 250mg/d apatinib as an initial dose,and 19 patients received an initial dose of 500mg/d apatinib enrolled in the high-dose group.It was found that patients in the high-dose group were more likely to have thrombocytopenia(P=0.010)and hypertension(P=0.004),which median PFS had no statistically significant(P=0.662).Conclusions1.Apatinib showed good efficacy in patients with recurrent epithelial ovarian cancer,especially in patients with platinum-resistant recurrent ovarian cancer who failed to multi-line chemotherapies.2.Apatinib showed good safety in the treatment of recurrent epithelial ovarian cancer.The most common adverse reactions included hypertension,hand-foot syndrome,proteinuria,fatigue,neutropenia and so on.Adverse reaction can predict the efficacy of apatinib,and hand-foot syndrome may be a predictor.3.Different doses of apatinib(500mg/d and 250mg/d)showed similar efficacy,but higher dose was a risk factor for thrombocytopenia and hypertension.