论文部分内容阅读
Background: Sequential SUN(tyrosine kinase inhibitor,TKI)until progression of disease(PD)followed by EVE(mTOR inhibitor)is standard therapy for patients with mRCC.This open-label,multicenter,phase Ⅱ trial compared 1st-line EVE to 1st-line SUN(NCT00903175).Sequential EVEiSUN was also compared with standard SUNiEVE.Methods: Patients with mRCC(clear or non-clear cell)na(i)ve to prior systemic therapy were randomized 1:1 to either 1st-line EVE 10 mg/day or SUN 50 mg/day(4 weeks on,2 weeks off)until PD.Patients then crossed over and continued on the alternate drug until PD.Primary objective was to assess PFS noninferiority of 1st-line EVE to 1st-line SUN; defined as an observed hazard ratio(HR)1st EVE/SUN #1.1.Overall survival(OS),combined 1st-line and 2nd-line PFS,and safety were secondary end points.Results: From10/09 to 6/11,471 patients enrolled(EVEiSUN,n 5 238; SUNiEVE,n 5 233).Median age was 62 years,85.4%had clear-cell RCC,and MSKCC favorable/intermediate/poor risk was 30/56/14%.Median follow-up was 22.7 months.A total of 53.7%of patients who discontinued 1st-line EVE entered into 2nd-line SUN and 51.6%of patients who discontinued 1st-line SUN entered into 2nd-line EVE.Median PFS(95%CI)was 7.9(5.6-8.2)months for 1st-line EVE and 10.7(8.2-11.5)months for 1st-line SUN.HR1st EVE/1st SUN(95%CI)was 1.43(1.15-1.77).Median OS(95%CI)was 22.4(19.7-NA)months for EVEiSUN and 32.0(20.5-NA)months for SUNiEVE; HREVE-SUN/SUN-EVE(95%CI)was 1.24(0.94-1.64).A trend in favor of SUNiEVE for OS was observed,but will need to be confirmed with final OS analysis.Additional efficacy results for secondary end points are forthcoming.Common treatmentemergent adverse events for 1st-line EVE vs SUN,respectively,were stomatitis(53%vs 57%),fatigue(45%vs 51%),and diarrhea(38%vs 57%).Conclusions: Noninferiority of PFS for 1st-line EVE compared with SUN was not achieved in this randomized phase Ⅱ trial of mRCC patients.The treatment paradigm remains SUNiEVE since the sequence achieved optimal clinical benefit.