依西美坦国际多中心研究课件.ppt

1、123Kaufmann,et al.J Clin Oncol.2000;18:1399-1411;Early Breast Cancer Trialists Collaborative Group.Lancet.2005;365:1687-1717.402040608010012014016000.10.20.30.40.50.60.70.80.91总生存概率总生存概率周周OS=总生存.Kaufmann,et al.J Clin Oncol.2000;18:1399-1411.依西美坦依西美坦P P-value-value0.0390.039E ENot ReachedNot ReachedM

2、M123.4123.4周周 醋酸甲地孕酮醋酸甲地孕酮5Early Breast Cancer Trialists Collaborative Group.Lancet.1998;351:1451-1467;Clemons,et al.Cancer Treat Rev.2004;30:325-332.6 Early Breast Cancer Trialists Collaborative Group.Lancet.1998;351:1451-1467.7Early Breast Cancer Trialists Collaborative Group.Lancet.2005;365:1687-

3、1717;Clemons,et al.Cancer Treat Rev.2004;30:325-332;Coombes RC,et al.N Engl J Med.2004;350:1081-1092.8Early Breast Cancer Trialists Collaborative Group.Lancet.2005;365:1687-1717.获得性耐药获得性耐药?910Note:Hypothetical Illustration.11122-3 2-3 年年2-3 2-3 年治疗研究年治疗研究诊断诊断研究开始研究开始共共5 5年的内分泌治疗年的内分泌治疗Coombes,ASCO 2

4、006.超过超过2 2年的治疗后随访年的治疗后随访13Coombes,ASCO 2006.*Intent-to-treat(ITT)population14Coombes,ASCO 2006.1516Coombes,ASCO 2006.17Coombes,ASCO 2006.1819End ofEnd oftreatmenttreatment0102030405060708090100012345Time since randomization(years)%surviving disease free意向治疗意向治疗354 events354 events2352 at risk2352 a

5、t risk454 events454 events2372 at risk2372 at riskCoombes,ASCO 2006.依西美坦依西美坦三苯氧胺三苯氧胺20有利于他莫昔芬有利于他莫昔芬有利于依西美坦有利于依西美坦风险比例风险比例(95%(95%CI)CI)ITT(E=20,T=35)ITT(E=20,T=35)出现对侧乳腺癌时间出现对侧乳腺癌时间 ER+/ER+/不明不明(E=238,T=285)E=238,T=285)远处复发时间远处复发时间无乳腺癌生存无乳腺癌生存无病生存无病生存0.40.40.60.60.80.81.01.01.21.2 ER+/ER+/不明不明(E=20

6、,T=35)E=20,T=35)ITT(E=249,T=297)ITT(E=249,T=297)ITT(E=354,T=454)ITT(E=354,T=454)ITT(E=289,T=374)ITT(E=289,T=374)ER+/ER+/不明不明(E=277,T=361)E=277,T=361)ER+/ER+/不明不明(E=339,T=438)E=339,T=438)0.75(0.65,0.87)0.75(0.64,0.87)0.82(0.69,0.98)0.56(0.33,0.98)0.76(0.66,0.88)0.76(0.65,0.88)0.83(0.70,0.98)0.57(0.33

7、,0.98)Coombes,ASCO 2006.HR(95%CI)HR(95%CI)21End ofEnd oftreatmenttreatment0102030405060708090100012345Time since randomization(years)%surviving disease freeER+/ER+/未明患者未明患者Coombes,ASCO 2006.339 events339 events2296 at risk2296 at risk依西美坦依西美坦他莫昔芬他莫昔芬438 events438 events2306 at risk2306 at risk22End

8、ofEnd oftreatmenttreatment0.000.050.100.150.200.25012345Time since randomization(years)Cumulative RateCoombes,ASCO 2006.354 events354 events2352 at risk2352 at risk454 events454 events2372 at risk2372 at risk依西美坦依西美坦他莫昔芬他莫昔芬意向治疗意向治疗 累计风险比例累计风险比例24Coombes,ASCO 2006.End oftreatmentER+/未明未明 累计风险比例累计风险比

9、例0.000.050.100.150.200.25012345Time since randomization(years)Cumulative Rate依西美坦依西美坦他莫昔芬他莫昔芬438 events2306 at risk339 events2296 at risk25Coombes,ASCO 2006.首发事件数首发事件数260.74(0.58,0.95)0.71(0.59,0.84)0.74(0.62,0.89)0.76(0.61,0.95)0.75(0.64,0.87)0.79(0.55,1.14)0.76(0.63,0.92)0.74(0.60,0.92)0.79(0.61,1

10、.03)0.68(0.54,0.85)0.83(0.64,1.07)0.74(0.64,0.85)0.74(0.64,0.85)CT=chemotherapy;CT=chemotherapy;*Adjusted for Nodal Status,Chemotherapy Use&HRT Use.Adjusted for Nodal Status,Chemotherapy Use&HRT Use.风险比例风险比例(95%(95%CI)CI)0.50.50.60.60.80.81.01.01.21.2 DFS(Adjusted)DFS(Adjusted)*年龄年龄 70 70 yrs(1153)y

11、rs(1153)年龄年龄 60-69 60-69 yrs(1969)yrs(1969)年龄年龄 60 2.5 yrs(1838)2.5 yrs(1838)先前他莫西芬先前他莫西芬=2.5 =2.5 yrs(2764)yrs(2764)ER ER 未明未明(560)(560)ER ER (4042)(4042)先前化疗先前化疗(1499)(1499)无先前化疗无先前化疗(3103)(3103)淋巴结阳性淋巴结阳性(2038)(2038)淋巴结阴性淋巴结阴性(2384)(2384)P0.0001P70 70 yrs(1153)yrs(1153)年龄年龄 60-69 60-69 yrs(1969)y

12、rs(1969)年龄年龄 60 2.5 2.5 yrs(1838)yrs(1838)先前他莫西芬先前他莫西芬 2.5 2.5 yrs(2764)yrs(2764)ER ER 未明未明(560)(560)ER ER(4042)(4042)先前化疗先前化疗(1499)(1499)未先前化疗未先前化疗(3103)(3103)淋巴结阴性淋巴结阴性(2038)(2038)淋巴结阳性淋巴结阳性(2384)(2384)风险比例风险比例(95%(95%CI)CI)0.50.50.60.60.80.81.01.01.21.21.51.5 CT=chemotherapy;CT=chemotherapy;*Adju

13、sted for Nodal Status,Chemotherapy Use&HRT Use.Adjusted for Nodal Status,Chemotherapy Use&HRT Use.Coombes,et al.ASCO 2006.P=0.04P=0.04HR(95%CI)HR(95%CI)32Coombes,ASCO 2006.*对于ER+/未明患者.33343536Coombes,ASCO 2006.37Data on File,Pfizer.依西美坦依西美坦他莫昔芬他莫昔芬潮热潮热 乏力乏力头痛头痛关节痛关节痛*21%21%16%16%13%13%13%13%20%20%15

14、%15%11%11%8%8%注:随访34.5 月.*统计学上显著性差异;治疗中出现的副作用.38Coombes,ASCO 2006.3922.1%v 20.9%1.8%v 1.8%1.0%v 0.8%2.5%v 2.4%1.9%v 3.1%*0.1%v 0.1%9.9%v 8.6%1.3%v 0.8%11.3%v 11.2%依西美坦依西美坦 v v 他莫昔芬他莫昔芬有利于他莫昔芬有利于他莫昔芬有利于依西美坦有利于依西美坦优势比优势比(99%(99%CI)CI)血栓血栓 其他其他 猝死猝死心血管意外心血管意外 外周血管病外周血管病 心衰心衰 心绞痛心绞痛 心梗心梗 心肌缺血心肌缺血所有的心血管和

15、血栓事件所有的心血管和血栓事件0.40.40.60.60.80.81.01.01.21.21.81.82.02.07.1%v 6.5%Coombes,ASCO 2006.*显著性差异.409.2%v 7.2%*17.5%v 14.6%*7.0%v 4.9%*0.6%v 0.4%0.6%v 0.2%1.1%v 1.3%5.0%v 3.4%*25.7%v 20.3%*20.8%v 15.1%*2.0%v 1.1%*2.5%v 4.4%*1.2%v 0.3%*2.8%v 0.4%*有利于他莫昔芬有利于他莫昔芬有利于依西美坦有利于依西美坦优势比优势比(99%(99%CI)CI)骨骼肌肉痛骨骼肌肉痛 腕

16、管腕管 胃溃疡胃溃疡 抽筋抽筋 关节僵直关节僵直关节痛关节痛关节炎关节炎(各型各型)骨质疏松骨质疏松 其他其他 腕骨腕骨脊椎脊椎 髋骨髋骨 骨折骨折0.40.40.80.8 1.01.02.02.03.03.0 4.04.06.06.0 8.08.00.60.6Coombes,ASCO 2006.依西美坦依西美坦 v v 他莫昔芬他莫昔芬*显著性差异.41有利于他莫昔芬有利于他莫昔芬有利于依西美坦有利于依西美坦6.4%v 9.8%*优势比优势比(99%(99%CI)CI)子宫内膜癌子宫内膜癌 刮宫刮宫子宫切除子宫切除子宫息肉子宫息肉/肌瘤肌瘤子宫内膜增生子宫内膜增生 阴道出血阴道出血 严重妇科事件严重妇科事件0.10.10.20.20.40.40.60.6 0.80.8 1.01.01.21.2Coombes,ASCO 2006.4.8%v 7.1%*0.2%v 1.0%*1.4%v 4.0%*0.9%v 1.5%0.7%v 1.5%*0.4%v 0.7%依西美坦依西美坦 v v 他莫昔芬他莫昔芬*显著性差异.42意向治疗意向治疗Coombes,ASCO 2006.43Coombes,ASCO 2006.44Coombes,ASCO 2006.4546