Clinical Efficacy And Safety Evaluation Of Axitinib And Its Dose Titration In The Treatment Of Metastatic Renal Cell Carcinoma

Objective:To analyze the clinical efficacy and adverse reactions of second line axitinib and its dose titration in the treatment of metastatic renal cell carcinoma,and explore the real-world status of axitinib in the treatment of metastatic renal cell carcinoma,so as to guide the choice of treatment options better for metastatic renal cell carcinoma.Methods:The clinical data of 66 patients with metastatic renal cell carcinoma were retrospectively analyzed who received second-line axitinib targeted therapy after failure of cytokine or first-line TKI targeted therapy at the Department of Urology,Xijing Hospital,Air Force Military Medical University,between January 2016 and January2021,including general information of patients,diagnosis and treatment,pathological types,imaging and examination data,survival status,adverse reactions and so on.All patients were divided into standard dose group(n=38)versus dose titration group(n=28)based on the axitinib targeted treatment strategy.The standard dose was 5 mg bid of oral axitinib;dose titration was to allow dose escalation after disease progression while receiving second-line axitinib targeted therapy.Statistics of baseline data and follow-up information of all patients were collected to evaluate the tumor efficacy according to the RECIST1.1 and Choi criteria,and the adverse reactions were analyzed using the CTCAE 5.0 criteria,which were classified as grades 1-5,among which grades 3-5 were serious adverse reactions.All data were analyzed by SPSS 25.0 software.Data of continuous variables were expressed by(±s)and analyzed by independent samples t-test,and the count data were described by rate(%)and analyzed byχ~2test,and survival curves were plotted and compared among different groups using the Kaplan Meier method.Results:A total of 66 patients with metastatic renal cell carcinoma who received second-line axitinib targeted therapy were enrolled,with a median follow-up of 28.5(3.0-40.0)months,a median PFS of 10.0 months,and a median OS of 29.0 months.The ORR improved by 25.7%based on the Choi evaluation criteria compared with the RECIST1.1 criteria(43.9%vs 18.2%,P=0.036),while the DCR was generally consistent(86.3%vs 87.9%,P=0.815).The median PFS and median OS in the dose titration group were 12.0 months(22.5 months vs 10.5 months,P<0.01)and 7 months(32.0 months vs 25.0 months,P<0.01)longer than that in the standard dose group,respectively.Overall adverse events associated with axitinib treatment in metastatic renal cell carcinoma were asthenia(68.2%,45/66),hypertension(41.1%,41/66),diarrhea(38.6%,38/66),and decreased appetite(37.1%,37/66),and were dominated by grade 1-2 adverse events.Grade 3 adverse reactions such as liver function abnormalities and proteinuria occurred in a small proportion of patients after titration,and the type and incidence of adverse reactions were slightly higher in the dose titration group.Conclusions:Axitinib,as a standard second line targeted agent for patients with metastatic renal cell carcinoma who have failed cytokine or TKI based therapy,has a controllable adverse reactions profile and reliable efficacy and safety.Dose titration confers additional survival benefits for patients with metastatic renal cell carcinoma.