来曲唑后续强化治疗培训课件

Click to edit Master text styles,Second level,Third level,Forth Level,Fifth Level,*,*,来曲唑后续强化治疗,*,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,*,来曲唑后续强化治疗,*,FEM-PM001/01-3/2010,Click to edit Master text styles,Second level,Third level,Forth Level,Fifth Level,*,来曲唑后续强化治疗,*,*,FEM-PM001/01-3/2010,Click to edit Master text styles,Second level,Third level,Forth Level,Fifth Level,*,来曲唑后续强化治疗,*,*,FEM-PM001/01-3/2010,Click to edit Master text styles,Second level,Third level,Forth Level,Fifth Level,*,来曲唑后续强化治疗,*,*,FEM-PM001/01-3/2010,Click to edit Master text styles,Second level,Third level,Forth Level,Fifth Level,*,来曲唑后续强化治疗,*,*,FEM-PM001/01-3/2010,Click to edit Master text styles,Second level,Third level,Forth Level,Fifth Level,*,来曲唑后续强化治疗,*,*,FEM-PM001/01-3/2010,Click to edit Master text styles,Second level,Third level,Forth Level,Fifth Level,*,来曲唑后续强化治疗,*,*,FEM-PM001/01-3/2010,Click to edit Master text styles,Second level,Third level,Forth Level,Fifth Level,*,来曲唑后续强化治疗,*,*,FEM-PM001/01-3/2010,Click to edit Master text styles,Second level,Third level,Forth Level,Fifth Level,*,来曲唑后续强化治疗,*,*,FEM-PM001/01-3/2010,Click to edit Master text styles,Second level,Third level,Forth Level,Fifth Level,*,来曲唑后续强化治疗,*,*,FEM-PM001/01-3/2010,Click to edit Master text styles,Second level,Third level,Forth Level,Fifth Level,*,来曲唑后续强化治疗,*,来曲唑后续强化治疗,MA17,试验可以回答的问题？,5,年他莫昔芬辅助治疗结束后，继续来曲唑治疗是否获益？,他莫昔芬辅助治疗结束后长期停药，重新开始来曲唑治疗是否获益？,谁将会从后续强化治疗中获益更多？,最佳的后续强化治疗持续时间？,1,来曲唑后续强化治疗,MA17,试验可以回答的问题？,5,年他莫昔芬辅助治疗结束后，继续来曲唑治疗是否获益？,他莫昔芬辅助治疗结束后长期停药，重新开始来曲唑治疗是否获益？,谁将会从后续强化治疗中获益更多？,最佳的后续强化治疗持续时间？,2,来曲唑后续强化治疗,NSABP B-14,试验：,延长他莫昔芬治疗无益,Fisher et al.,J Natl Cancer Inst,.2001;93:684-690.,TAM,长期应用子宫内膜癌、缺血性心脏病和缺血性脑血管病发生率更高,P,=0.03,无病生存率,100,90,80,70,60,50,%,0,1,2,3,4,5,6,7,患者数,事件数,安慰剂,569 106,他莫昔芬,583 137,P,=0.07,总生存率,死亡患者数,39,57,0,1,2,3,4,5,6,7,82%,78%,94%,91%,3,来曲唑后续强化治疗,MA.17,试验：试验设计,主要终点：,DFS,次要终点：,OS/,安全性,/,生活质量亚组研究：骨密度（,BMD,）,/,骨标记物、血脂谱,随机分组,a,他莫昔芬,安慰剂,qd,b,来曲唑,2.5 mg qd,a,近,5,年的辅助治疗,5,年后续辅助治疗,0-3,个月,n=2575,n=2582,a,n=2575(,疗效,),2154(,安全性,);,b,n=2582(,疗效,),2145(,安全性,),Goss et al.,N Engl J Med,.2003;349:1793;Goss et al.,J Natl Cancer Inst,.2005;97:1262.,确诊乳腺癌,(N=5157),绝经后,ER+,和,/,或,PgR+,任何淋巴结状态,ECOG PS,：,0-2,在随机分组时无复发,4,来曲唑后续强化治疗,MA.17,试验：早期和最终分析,早期分析,1,中位随访：,27.5,个月,DFS,：,HR:0.61;,P,0.001,OS,：,HR:0.76;,P,=0.25,试验揭盲，安慰剂组可以接受来曲唑治疗,最终分析,2,中位随访：,30,个月,DFS,：,HR=0.58,；,P,0.001,DDFS,：,HR=0.60,；,P,0.002,OS:HR=0.82,；,P,=0.3,1.Goss et al.N Engl J Med.2003;349:1793.2.Goss et al.J Natl Cancer Inst.2005;97:1262.,5,来曲唑后续强化治疗,他莫昔芬,N=5187,5,年,中位随访时间,(,月,),30,月,ITT,分析,64,月,ITT,分析,来曲唑,n=2593,2003,年,10,月，,MA17,试验中期分析公布，文章公开发表在,N Engl J Med,上,由于来曲唑的卓越疗,IDMC,要求试验提前揭盲，随后,2/3,的安慰剂组患者换药来曲唑治疗,0-3,个月,R,Goss et al.,J Clin Oncol.,2008;26:1948.,安慰剂,n=2594,MA17,揭盲后,ITT,分析,来曲唑,(PLAC-LET)n=1579,来曲唑,n=2457,安慰剂,(,PLAC,)n=804,54,月,ITT,分析,27.5,月,ITT,分析,6,来曲唑后续强化治疗,MA.17,试验,:54,个月,ITT,分析,Update of Ingle et al.,J Clin Oncol.,2006;24(18S):15s.Abstract 549.,HR=,风险比；,CI=,可信区间,;DFS=,无病生存；,DDFS=,无远处转移生存；,OS=,总生存,；,CBC=,对侧乳腺癌,所有随机分组的患者,HR(95%CI),来曲唑,vs,安慰剂,P,值,*,DFS,DDFS,OS,CBC,0.64(0.52-0.79),0.76(0.58-0.99),1.00(0.78-1.27),0.61(0.38-0.98),0.00003,0.045,0.97,0.037,尽管,2/3,的安慰剂组的患者转为来曲唑治疗，仍然可以看到初始来曲唑组的疗效优势,7,来曲唑后续强化治疗,MA.17,试验：,64,个月,ITT,分析,所有随机分组的患者,HR(95%CI),来曲唑,vs,安慰剂,P,值,a,DFS,DDFS,OS,CBC,0.68(0.56-0.83),0.81(0.63-1.03),0.98(0.78-1.22),0.61(0.39-0.97),0.0001,0.089,0.828,0.033,b,a,多变量分析；包括所有因素的分层,Cox,回归分析,b,包括试验分层因素（受体状态、淋巴结状态、之前接受的辅助化疗）的分层时序检验,Ingle et al.,Ann Oncol.,2008;19:877.,尽管,2/3,的安慰剂组的患者转为来曲唑治疗，仍然可以看到初始来曲唑组的疗效优势,8,来曲唑后续强化治疗,MA 17 ITT,分析小结,27.5,个月的结果显示来曲唑后续强化治疗疗效显著，导致了试验的早期揭盲,长期随访中，尽管安慰剂组有,2/3,的患者换用来曲唑，,ITT,分析中仍然显示,DFS,的优势,因此，来曲唑后续强化治疗对控制早期乳腺癌辅助治疗,5,年后的复发至关重要，已被,St Gallen,和,NCCN,等指南推荐,9,来曲唑后续强化治疗,MA17,试验可以回答的问题？,5,年他莫昔芬辅助治疗结束后，继续来曲唑治疗是否获益？,他莫昔芬辅助治疗结束后长期停药，重新开始来曲唑治疗是否获益？,谁将会从后续强化治疗中获益更多？,最佳的后续强化治疗持续时间？,10,来曲唑后续强化治疗,他莫昔芬,N=5187,5,年,中位随访时间,(,月,),30,64,来曲唑,n=2593,揭盲,目的：在他莫昔芬治疗后一段时间（,1-7,年）才开始来曲唑治疗比较,PLAC-LET vs PLAC,的疗效和安全性,非随机的探索性研究,揭盲后的治疗组的基线特征不同，并且,PLAC-LET,组患者具有较高的复发风险。由于存在不均衡，因此对主要变量进行多变量分析,0-3,个月,LEA,报告,R,Goss et al.,J Clin Oncol.,2008;26:1948.,安慰剂,n=2594,MA.17,试验：延迟后续辅助治疗,试验设计和入组人群,来曲唑,(PLAC-LET)n=1579,来曲唑,n=2457,安慰剂,(,PLAC,)n=804,11,来曲唑后续强化治疗,MA.17,试验：延迟后续辅助治疗,疗效结果,a,P,0.0001,P,=0.004,P,0.0001,P,=0.004,DFS,DDFS,OS,CBC,a,对基线特征不同的非随机患者进行探索性分析,Goss et al.,J Clin Oncol.,2008;26:1948.,从原始随机分组的时间开始进行计算，排除揭盲前死亡或者复发的患者,与安慰剂相比风险,的降低程度,(%),12,来曲唑后续强化治疗,MA.17,试验：延迟后续辅助治疗,结论,绝经后激素依赖性乳腺癌患者在完成他莫昔芬治疗后一段时间（,1-7,年）才开始接受来曲唑后续辅助治疗，仍能获得,DFS,、,DDFS,、,OS,的显著改善，因此这类人群应考虑接受这种治疗方案的治疗,Goss et al.,J Clin Oncol.,2008;26:1948.,13,来曲唑后续强化治疗,MA17,试验可以回答的问题？,5,年他莫昔芬辅助治疗结束后，继续来曲唑治疗是否获益？,他莫昔芬辅助治疗结束后长期停药，重新开始来曲唑治疗是否获益？,谁将会从后续强化治疗中获益更多？,最佳的后续强化治疗持续时间？,14,来曲唑后续强化治疗,后续强化治疗中谁将获益更多？,考虑因素,淋巴结状态,初诊时月经状态,15,来曲唑后续强化治疗,淋巴结阳性患者,HR 0.61*,(95%CI,0.45-0.84),HR 0.53*,(95%CI,0.36-0.78),HR 0.61*,(95%CI,0.38-0.98),所有患者,DFS*,HR 0.58;,P,0.001,Distant DFS*,HR 0.60;,P,0.002,OS,HR 0.82;,P,=0.3,淋巴结阴性患者,HR 0.45*,(95%CI,0.27-0.75),HR 0.63,(95%CI,0.31-1.27),HR 1.52,(95%CI,0.76-3.