复发或转移性乳腺癌治疗策略规范课件.ppt

1、 妇女最常见的恶性肿瘤，全球每年新诊断乳腺癌妇女最常见的恶性肿瘤，全球每年新诊断乳腺癌 120 120 万，死亡约万，死亡约5050万。北美、北欧为高发区，女性癌症死亡万。北美、北欧为高发区，女性癌症死亡 的第二位，为亚洲地区的的第二位，为亚洲地区的4 4倍倍。我国女性乳腺癌发病率明显增高，尤其是北京、上海、我国女性乳腺癌发病率明显增高，尤其是北京、上海、天津等大城市。上海天津等大城市。上海9090年代发病率为年代发病率为38/1038/10万，为女性恶万，为女性恶 性肿瘤的第性肿瘤的第1 1位位。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

2、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

3、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内分泌治疗失败失败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A vs T vs ATTTFOSOShaughnessy J,et al.J Clin Oncol,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;lba

4、in 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=0.0489ProbabilityHR=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 42 481.00.80.60.40.20.0MonthsTGTPro

5、babilityAlbain 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(months)N EventsMedian(95%CI)1531518.05 (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 Probabilit

6、y1.00.80.60.40.20.0D,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 assessedChan 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

7、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.2001Melemed 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.2005C

8、han 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;20:281223;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 a

9、t ASCO Breast Cancer 2007;Avastin Summary of Product Characteristics客观缓解率(%)单药紫杉醇010203040506070DocetaxelChan 1999DoxorubicinChan 1999PaclitaxelSeidman 2004VinorelbineMuhoz 2006Doxorubicin+paclitaxelJassem 2001Capecitabine+docetaxelOShaughnessy 2002Gemcitabine+paclitaxelAlbain 2004Fluorouracil+epiru

10、bicinZielinski 2005Gemcitabine+vinorelbineMuoz 2006Epirubicin+taxanePacilio 2006Avastin+paclitaxelE2100 2005PaclitaxelE2100 200502468101214MonthsMonotherapyCombinationchemotherapy chemotherapy+targeted therapyMedian PFS/TTP9 monthsEMEA Avastin European Public Assessment Report,2007Patients with heav

11、ily pretreated locally recurrent or metastatic breast cancer(N=762)Eribulin Mesylate1.4 mg/m2 2-5 min IV on Days 1,8 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;strat

12、ified by geographic region,previous capecitabine treatment,HER2/neu statusTwelves C,et al.ASCO 2010.Abstract CRA1004.*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.Abs

13、tract CRA1004.13.1210.653.62.2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.

14、8%20.3%38.4%37.8%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%)7

15、8(48%)中位中位PFS(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)0.017AVADO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;C,capecitabine;P,pertuzumab;L,lapatinib;