馮奉儀復(fù)發(fā)或轉(zhuǎn)移性乳腺癌的治療策略課件

1、馮奉儀復(fù)發(fā)或轉(zhuǎn)移性乳腺癌的治療策略1馮奉儀復(fù)發(fā)或轉(zhuǎn)移性乳腺癌的治療策略2 婦女最常見的惡性腫瘤，全球每年新診斷乳腺癌婦女最常見的惡性腫瘤，全球每年新診斷乳腺癌 120 120 萬，死亡約萬，死亡約5050萬。北美、北歐為高發(fā)區(qū)，女性癌癥死亡萬。北美、北歐為高發(fā)區(qū)，女性癌癥死亡 的第二位，為亞洲地區(qū)的的第二位，為亞洲地區(qū)的4 4倍倍。 我國女性乳腺癌發(fā)病率明顯增高，尤其是北京、上海、我國女性乳腺癌發(fā)病率明顯增高，尤其是北京、上海、 天津等大城市。上海天津等大城市。上海9090年代發(fā)病率為年代發(fā)病率為38/1038/10萬，為女性惡萬，為女性惡 性腫瘤的第性腫瘤的第1 1位位。馮奉儀復(fù)發(fā)或轉(zhuǎn)移性乳

2、腺癌的治療策略3馮奉儀復(fù)發(fā)或轉(zhuǎn)移性乳腺癌的治療策略4馮奉儀復(fù)發(fā)或轉(zhuǎn)移性乳腺癌的治療策略5 細胞毒藥物細胞毒藥物蒽環(huán)類蒽環(huán)類紫杉類紫杉類卡培他濱卡培他濱長春瑞濱長春瑞濱吉西他濱吉西他濱 激素類藥物激素類藥物三苯氧胺三苯氧胺芳香化酶抑制劑芳香化酶抑制劑fulvestrantfulvestrantlhrh lhrh 拮抗劑拮抗劑靶向治療靶向治療 egfregfr抑制抑制: :trastuzumabtrastuzumab,pertuzumab?,pertuzumab? t-dm1? t-dm1? 信號傳導(dǎo)抑制劑信號傳導(dǎo)抑制劑: :lapatiniblapatinib gefetinib? erloti

3、nib?gefetinib? erlotinib? 血管生成抑制劑血管生成抑制劑: :bevacizumabbevacizumab雙磷酸鹽類雙磷酸鹽類支持與姑息治療支持與姑息治療馮奉儀復(fù)發(fā)或轉(zhuǎn)移性乳腺癌的治療策略6內(nèi)分泌治療內(nèi)分泌治療化療化療靶向治療靶向治療靶向治療靶向治療馮奉儀復(fù)發(fā)或轉(zhuǎn)移性乳腺癌的治療策略7復(fù)發(fā)或轉(zhuǎn)移性乳腺癌復(fù)發(fā)或轉(zhuǎn)移性乳腺癌er和或和或pr 陽性陽性內(nèi)分泌治療內(nèi)分泌治療er和或和或pr陰性陰性化療化療內(nèi)分泌治療內(nèi)分泌治療失敗失敗her2陽性陽性化療化療+曲妥珠單抗曲妥珠單抗her2 陰性陰性化療化療化療化療+拉帕替尼拉帕替尼馮奉儀復(fù)發(fā)或轉(zhuǎn)移性乳腺癌的治療策略8馮奉儀復(fù)發(fā)或轉(zhuǎn)

4、移性乳腺癌的治療策略9馮奉儀復(fù)發(fā)或轉(zhuǎn)移性乳腺癌的治療策略10馮奉儀復(fù)發(fā)或轉(zhuǎn)移性乳腺癌的治療策略11馮奉儀復(fù)發(fā)或轉(zhuǎn)移性乳腺癌的治療策略12馮奉儀復(fù)發(fā)或轉(zhuǎn)移性乳腺癌的治療策略13a vs t vs atttfttfosos馮奉儀復(fù)發(fā)或轉(zhuǎn)移性乳腺癌的治療策略14馮奉儀復(fù)發(fā)或轉(zhuǎn)移性乳腺癌的治療策略15oshaughnessy j, et al. j clin oncol, 2002; 20: 2812-2823.ttp os xt (n=255) 42% t (n=256)30%orrp=0.006馮奉儀復(fù)發(fā)或轉(zhuǎn)移性乳腺癌的治療策略160 6 12 18 24 30 36 42 481.00.80.6

5、0.40.20.0overall 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=0.0489probability馮奉儀復(fù)發(fā)或轉(zhuǎn)移性乳腺癌的治療策略17hr = 0.70 (95% ci: 0.59 , 0.85)logrank p=0.0002event

6、s227237median (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.與紫杉醇相比，健擇與紫杉醇相比，健擇聯(lián)合紫杉醇可顯著延長聯(lián)合紫杉醇可顯著延長馮奉儀復(fù)發(fā)或轉(zhuǎn)移性乳腺癌的治療策略18albain et al. j clin oncol 2008;26(24):x-x.馮奉儀復(fù)發(fā)或轉(zhuǎn)移性乳腺癌的治療策略19progression free survival

7、 (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 d c 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,

8、 texas.馮奉儀復(fù)發(fā)或轉(zhuǎn)移性乳腺癌的治療策略2020*investigator assessedchan s et al. presented at: san antonio breast cancer conference, december 13-16, 2007; san antonio, texas.馮奉儀復(fù)發(fā)或轉(zhuǎn)移性乳腺癌的治療策略21gdc較較cd gg方案二線治療方案二線治療階段及總的階段及總的ttp更長更長注：健擇 在中國批準的適應(yīng)癥為聯(lián)合紫杉醇治療復(fù)發(fā)或轉(zhuǎn)移性乳腺癌馮奉儀復(fù)發(fā)或轉(zhuǎn)移性乳腺癌的治療策略22marty et al. 2005紫杉醇 + 健擇紫杉醇 + 赫賽汀多

9、西紫杉醇+ 健擇多西紫杉醇+ 赫賽汀單藥多西紫杉醇多西紫杉醇希羅達slamon et al. 2001melemed et al. 2007e2100 2007紫杉醇 + 貝伐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*僅包括有可測量病灶的患者slamon dj, et al. n e

10、ngl 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 at asco breast cancer 2007; ava

11、stin summary of product characteristics客觀緩解率 (%)單藥紫杉醇010203040506070馮奉儀復(fù)發(fā)或轉(zhuǎn)移性乳腺癌的治療策略23docetaxelchan 1999doxorubicinchan 1999paclitaxelseidman 2004vinorelbinemuhoz 2006doxorubicin + paclitaxeljassem 2001capecitabine + docetaxeloshaughnessy 2002gemcitabine + paclitaxelalbain 2004fluorouracil + epirub

12、icinzielinski 2005gemcitabine + vinorelbinemuoz 2006epirubicin + taxanepacilio 2006avastin + paclitaxele2100 2005paclitaxele2100 200502468101214monthsmonotherapycombinationchemotherapy chemotherapy +targeted therapymedian pfs/ttp9 monthsemea avastin european public assessment report, 2007馮奉儀復(fù)發(fā)或轉(zhuǎn)移性乳腺

13、癌的治療策略24patients with heavily 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 ca

14、re only(n = 254)randomized 2:1; stratified 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 receiv

15、ed chemotherapy馮奉儀復(fù)發(fā)或轉(zhuǎn)移性乳腺癌的治療策略25twelves c, et al. asco 2010. abstract cra1004.13.1213.1210.6510.653.63.62.22.2馮奉儀復(fù)發(fā)或轉(zhuǎn)移性乳腺癌的治療策略26馮奉儀復(fù)發(fā)或轉(zhuǎn)移性乳腺癌的治療策略27馮奉儀復(fù)發(fā)或轉(zhuǎn)移性乳腺癌的治療策略28馮奉儀復(fù)發(fā)或轉(zhuǎn)移性乳腺癌的治療策略29馮奉儀復(fù)發(fā)或轉(zhuǎn)移性乳腺癌的治療策略30哈里森腫瘤學(xué)手冊. 人民軍醫(yī)出版社2010年9月第一版.馮奉儀復(fù)發(fā)或轉(zhuǎn)移性乳腺癌的治療策略31no. of patientscr + pr, % 61 vs 59 44 vs 14325

16、 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%37.8%40.5%49.3% kaufman et al 2006馮奉儀復(fù)發(fā)或轉(zhuǎn)移性乳腺癌的治療策略43 trastuzumab +chemoth

17、erapyher2+ /er + mbcgood performance statusvisceral diseaserapidly progressingpoor performance statusnon visceral diseaseslow progression trastuzumabmonotherapy trastuzumab +aromatase inhibitorprior a.i.?yesno馮奉儀復(fù)發(fā)或轉(zhuǎn)移性乳腺癌的治療策略44病人數(shù)病人數(shù)160160161161進展或死亡進展或死亡60(38%)60(38%)78(48%)78(48%)中位中位pfs(pfs(月月)

18、)8.48.44.44.4 hazard ratio (95% hazard ratio (95% ci)ci)0.49 (0.34-0.71)0.49 (0.34-0.71) p p值值(log-rank,1-side)(log-rank,1-side) 0.001 0.001蒽環(huán)、紫彬、蒽環(huán)、紫彬、 trastuzumabtrastuzumab治療失敗患者治療失敗患者orr(95%ci) 28.8% (21.9-36.4) orr(95%ci) 28.8% (21.9-36.4) 16.1% (10.8-22.8)16.1% (10.8-22.8) p p值值(fisher,s exact, 2-sided) (fisher,s exact, 2-sided) 0.0170.017馮奉儀復(fù)發(fā)