复发或转移性乳腺癌治疗的选择课件整理.ppt

1、复发或转移性乳腺癌治疗的选择 细胞毒药物细胞毒药物蒽环类蒽环类紫杉类紫杉类卡培他滨卡培他滨长春瑞滨长春瑞滨吉西他滨吉西他滨 激素类药物激素类药物三苯氧胺三苯氧胺芳香化酶抑制剂芳香化酶抑制剂FulvestrantFulvestrantLHRH LHRH 拮抗剂拮抗剂靶向治疗靶向治疗 EGFREGFR抑制抑制:TrastuzumabTrastuzumab,Pertuzumab?,Pertuzumab?T-DM1?T-DM1?信号传导抑制剂信号传导抑制剂:Lapatinib Gefetinib?Erlotinib?血管生成抑制剂血管生成抑制剂:BevacizumabBevacizumab双磷酸盐类双

2、磷酸盐类支持与姑息治疗支持与姑息治疗内分泌治疗内分泌治疗化疗化疗靶向治疗靶向治疗靶向治疗靶向治疗复发或转移性乳腺癌复发或转移性乳腺癌ER和或和或PR 阳性阳性内分泌治疗内分泌治疗ER和或和或PR阴性阴性化疗化疗内分泌治疗失败内分泌治疗失败HER2阳性阳性化疗化疗+曲妥珠单抗曲妥珠单抗HER2 阴性阴性化疗化疗化疗化疗+拉帕替尼拉帕替尼ASCO 2010.US Oncology(IHC3+population)0 9.一般状况较差，无症状的转移的患者，可能更从单药序贯治疗中获益。Chemotherapy010203040506070ASCO 2010.(chemotherapeutic,horm

3、onal,or biological),*6mg用于绝经前/围绝经期晚期乳腺癌：期临床试验复发或转移性乳腺癌首选化疗方案1st-lineHerceptinJ Clin Oncol 2008;26(24):X-X.蒽环、紫彬、Trastuzumab治疗失败患者XT(n=255)42%Paridaens et al.Avastin+paclitaxelE2100 2005Vagel T 114 26;FISH+35 3.Total responses(%)10%初诊时即为转移性乳腺癌0001 25.A vs T vs ATTTFOSOShaughnessy J,et al.J Clin Oncol

4、,2002;20:2812-2823.TTP OS XT(n=255)42%T(n=256)30%ORRp=0.0060 6 12 18 24 30 36 42 481.00.80.60.40.20.0Overall Survival Time(months)G,GEM;T,PTX;lbain et al.J Clin Oncol 2008;26(24):X-X.18219518.6(16.6,20.7)15.8(14.4,17.4)TGTN Events Median(95%CI)266263HR=0.82(95%CI:0.67,1.00)Log rank p=0.0489Probabili

5、tyHR=0.70(95%CI:0.59,0.85)Logrank p=0.0002Events227237Median(95%CI)6.1(5.3,6.7)4.0(3.5,4.4)0 6 12 18 24 30 36 42 481.00.80.60.40.20.0MonthsTGTProbabilityAlbain et al.J Clin Oncol 2008;26(24):X-X.与紫杉醇相比，健择与紫杉醇相比，健择联合紫杉醇可显著延长联合紫杉醇可显著延长Albain et al.J Clin Oncol 2008;26(24):X-X.Progression Free Survival

6、(months)N EventsMedian(95%CI)531518.05 (6.60,8.71)1521427.98 (6.93,8.77)Log rank p=0.121HR=1.20(95%CI:0.96,1.50)GD CD0 10 20 30 40 50 Probability1.00.80.60.40.20.0D,DTX;G,GEM;C,Cape Chan S et al.Presented at:San Antonio Breast Cancer Conference,December 13-16,2007;San Antonio,Texas.20*Investigator a

7、ssessedChan S et al.Presented at:San Antonio Breast Cancer Conference,December 13-16,2007;San Antonio,Texas.GDC较较CD G方案二线治疗方案二线治疗阶段及总的阶段及总的TTP更长更长注：健择 在中国批准的适应症为联合紫杉醇治疗复发或转移性乳腺癌健择联合多西紫杉醇 vs.Jones et al.Jones et al.目前最有效的乳腺癌化疗方案之一Anastrozole 1 mg蒽环、紫彬、Trastuzumab治疗失败患者Study Regimen No.RR（CR)ORR(95%CI

8、)28.Francisco J.ProbabilityMarty et al.):24s(Abstract 581);Melemed AS,et al.Abstract CRA1004.Abstract 1005.(first-line)与紫杉醇相比，健择联合紫杉醇可显著延长TTPTrastuzumab治疗HER2阳性转移性乳腺癌方案存在广泛转移,特别是内脏转移（肝,肺）25 mg vs TAM存在广泛转移,特别是内脏转移（肝,肺）Marty et al.2005紫杉醇+健择紫杉醇+赫赛汀多西紫杉醇+健择多西紫杉醇+赫赛汀单药多西紫杉醇多西紫杉醇希罗达Slamon et al.2001Mele

9、med et al.2007E2100 2007紫杉醇+贝伐Jones et al.2005Melemed et al.2007E2100 2007Slamon et al.2001Jones et al.2005Marty et al.2005OShaughnessy et al.2002OShaughnessy et al.2002Chan et al.2005Chan et al.2005*仅包括有可测量病灶的患者Slamon DJ,et al.N Engl J Med 2001;344:78392;OShaughnessy J,et al.J Clin Oncol 2002;20:28

10、1223;Jones SE,et al.J Clin Oncol 2005;23:554251;Marty M,et al.J Clin Oncol 2005;23:426574;Chan S,et al.J Clin Oncol 2005;23(June 1 suppl.):24s(Abstract 581);Melemed AS,et al.Presented at ASCO Breast Cancer 2007;Avastin Summary of Product Characteristics客观缓解率(%)单药紫杉醇010203040506070DocetaxelChan 1999D

11、oxorubicinChan 1999PaclitaxelSeidman 2004VinorelbineMuhoz 2006Doxorubicin+paclitaxelJassem 2001Capecitabine+docetaxelOShaughnessy 2002Gemcitabine+paclitaxelAlbain 2004Fluorouracil+epirubicinZielinski 2005Gemcitabine+vinorelbineMuoz 2006Epirubicin+taxanePacilio 2006Avastin+paclitaxelE2100 2005Paclita

12、xelE2100 200502468101214MonthsMonotherapyCombinationchemotherapy chemotherapy+targeted therapyMedian PFS/TTP9 monthsEMEA Avastin European Public Assessment Report,2007Patients with heavily pretreated locally recurrent or metastatic breast cancer(N=762)Eribulin Mesylate1.4 mg/m2 2-5 min IV on Days 1,

13、8 q3w(n=508)Treatment of Physicians Choice(TPC)Any monotherapy approved for cancer treatment(chemotherapeutic,hormonal,or biological),*or supportive care only(n=254)Randomized 2:1;stratified by geographic region,previous capecitabine treatment,HER2/neu statusTwelves C,et al.ASCO 2010.Abstract CRA100

14、4.*FDA approved for the treatment of cancer.Palliative treatment or radiotherapy according to local practice.96%of patients in TPC arm received chemotherapyTwelves C,et al.ASCO 2010.Abstract CRA1004.13.1210.653.62.2(%)P (M)P (M)PAromatase InhibitorCapecitabine+docetaxelOShaughnessy 2002ORR(95%CI)28.

15、Fluorouracil+epirubicinZielinski 2005蒽环类成为辅助治疗基本药物后，复发或转移性乳腺癌的一线治疗？20(95%CI:0.AC(ADM+CTX)复发或转移性乳腺癌首选化疗方案EMILIA III 580(2线)T-DM1 PFS 随机Bangemann et al.70末 蒽环类药单药化疗 3050(10）(chemotherapeutic,hormonal,or biological),*monotherapy复发或转移性乳腺癌治疗与紫杉醇相比，健择联合紫杉醇可显著提高ORRvs C+L Safety1st-lineHerceptinUS Oncology(

16、IHC3+population)哈里森肿瘤学手册.人民军医出版社2010年9月第一版.No.of patientsCR+PR,%61 vs 59 44 vs 14325 vs 32621.1 vs 17453 vs 45430 vs 20*Clin.Benefit,%55 vs 39*59.1 vs 45.6*49 vs 38*Median TTP,mo 8.9 vs 5.2 8.5 vs 7.0 9.4 vs 6.0*OS:not significant,*P6 months);PD,progressive disease0102030405060PRSDPD6.8%20.3%38.4%37

17、.8%40.5%49.3%Kaufman et al 2006 Trastuzumab+ChemotherapyHER2+/ER+MBCGood performance statusVisceral diseaseRapidly progressingPoor performance statusNon visceral diseaseSlow progression Trastuzumabmonotherapy Trastuzumab+Aromatase InhibitorPrior A.I.?YESNO病人数病人数160161进展或死亡进展或死亡60(38%)78(48%)中位中位PFS(

18、月月)8.44.4 Hazard Ratio(95%CI)0.49(0.34-0.71)P值值(log-rank,1-side)0.001蒽环、紫彬、蒽环、紫彬、Trastuzumab治疗失败患者治疗失败患者ORR(95%CI)28.8%(21.9-36.4)16.1%(10.8-22.8)p值值(Fisher,s exact,2-sided)0.0174)16.1980s 含蒽环类药联合化疗 5070（1015）OS:not significant,*P0.N Events Median(95%CI)4)16.单药序贯化疗或联合化疗复发或转移性乳腺癌治疗蒽环、紫彬、Trastuzumab治疗

19、失败患者与紫杉醇相比，健择联合紫杉醇可显著延长OSSlamon AC or P+T vs.Trastuzumab一线治疗HER2阳性乳腺癌Patients(%)Melemed et al.注：健择在中国批准的适应症为联合紫杉醇治疗复发或转移性乳腺癌6mg+Eur J Cancer Part A +三苯氧胺 三苯氧胺1995;31A:13742.ASCO 2010.ASCO 2010.Cancer 2001;92:224758CombinationchemotherapyLogrank p=0.AVADO多西紫杉醇E2100紫杉醇RIBBON-1,2卡培他滨，紫杉类或蒽环类随机入组仅化疗化疗+贝

20、伐单抗直至进展选择性二线治疗：化疗+贝伐单抗（AVADO 和RIBBON-1）初治初治的转的转移性移性乳腺乳腺癌癌Joyce OShaughnessy et al,ASCO 2010,abs 1005 OShaughnessy J,et al.ASCO 2010.Abstract 1005.*Assessed in patients with measurable disease at baseline:n=1105 for chemotherapy plus bevacizumab;n=788 for chemotherapy alone.D,docetaxel;T,trastuzumab;

21、C,capecitabine;P,pertuzumab;L,lapatinib;HER2+/ER+6mg用于绝经前/围绝经期晚期乳腺癌：期临床试验6mg 卵巢切除术Ann Oncol 或 卵巢照射 或 卵巢照射 1994;5:33742.复发或转移性乳腺癌首选化疗方案Abstract 1005.GDBangemann et al.J Clin Oncol 2008;26(24):X-X.Kaufman et al 2006D,docetaxel;T,trastuzumab;C,capecitabine;P,pertuzumab;L,lapatinib;T(n=256)30%ASCO 2010.Bonneterre et al.96%of patients in TPC arm received chemotherapyTwelves C,et al.Avastin+paclitaxelE2100 2005卡培他滨，紫杉类或蒽环类DoxorubicinChan 1999TDM4788g III 1092(1线)T-DM1+P PFS 隨机双盲J Clin Oncol 2005;23(June 1 suppl.Trastuzumab一线治疗HER2阳性乳腺癌