晚期HR+ HER2-乳腺癌内分泌治疗的几点思考

,晚期HR+HER2-乳腺癌内分泌治疗的几点思考,化疗or内分泌治疗？,1,用哪种药物？,2,持续多长时间？,3,一线治疗方案的选择,复发,化疗or内分泌治疗？,远处,局部,区域,内脏,其他,危及生命,CT,ET,有or无？TAMorAI?,12个月or12个月？,PreorPeriorPost？,辅助内分泌药物,无病间期,月经状态,用哪种药物？,绝经后乳腺癌,一线内分泌药物使用哪个是合理的,持续多久,一直用到有进展的明确证据,PALOMA-1和PALOMA-2的结果支持Palbociclib+来曲唑应用于一线内分泌治疗4。,对于一线内分泌治疗，托瑞米芬和他莫昔芬的效果相似，副作用也相当3。,FIRST,FALCON的结果，支持氟维司群应用于一线内分泌治疗2。,对于一线内分泌治疗，第三代AI的几种药物效果相当，来曲唑可能更好1。,1.CochraneDatabaseSystRev.2009Oct7;(4):CD003370.2.Lancet.2016Dec17;388(10063):2997-30053.CochraneDatabaseSystRev.2012Jul11;(7):CD008926.4.LancetOncol.2015Jan;16(1):25-35.,相关证据,BOLERO-2的结果支持依维莫司+依西美坦应用于一线内分泌治疗（Progressedwithin12mooronnonsteroidalAI,oranytimeontamoxifen)1。,BOLERO-4的结果支持依维莫司+来曲唑应用于一线内分泌治疗。,1.NEnglJMed.2012Feb9;366(6):520-9.2.LancetOncol.2016Apr;17(4):425-39.3.,用哪种药物？,Al(nonsteroidal)FulvestrantAl+palbociclibTamoxifen,FulvestrantpalbociclibAl+everolimusAl(steroidal)Tamoxifen,Al(nonsteroidal)Al+fulvestrantAl+palbociclibTamoxifen,Al(nonsteroidal)FulvestrantAl+palbociclib,Al,nonsteroidalpreferredAl+fulvestrantAl+palbociclib,Laterelapse(12monthssinceadjuvanttherapy),Earlyrelapse(12monthssinceadjuvanttherapy),Laterelapse(12monthssinceadjuvanttherapy),Earlyrelapse(12monthssinceadjuvanttherapy),PriortreatmentwithanAl,Priortreatmentwithtamoxifen,Prioradjuvantendocrinetherapy,Noprioradjuvantendocrinetherapy,Premenopausal,所有的病人都需要OFS?,哪种药物与OFS搭档最好？,什么时候开始用OFS用哪种OFS？,绝经前乳腺癌,对于绝经前HR+MBC目前缺少大宗的数据指导。,对于绝经前HR+MBC，ET+OFS应作为优选。,未接受辅助内分泌治疗的绝经前HR+MBC应接受OFS+TAM/AI。,对于辅助ET方案为TAM的绝经前HR+MBC,若在辅助治疗期间或者辅助治疗结束后12个月内复发，应接受OFS+AI。,4,1,2,3,GnRH？,手术切除？,现有的证据表明，手术切除和GnRH对卵巢功能的抑制效果相当。,但是ASCO晚期乳腺癌内分泌指南和ESMO晚期乳腺癌专家共识都强调要重视GnRH对卵巢功能抑制不完全的风险1,2。,1.JClinOncol.2016Sep1;34(25):3069-103.2.AnnOncol.2017Jan1;28(1):16-33.,用哪种药物？,Al(nonsteroidal)FulvestrantAl+palbociclibTamoxifen,FulvestrantpalbociclibAl+everolimusAl(steroidal)Tamoxifen,Al(nonsteroidal)Al+fulvestrantAl+palbociclibTamoxifen,Al(nonsteroidal)FulvestrantAl+palbociclib,Al,nonsteroidalpreferredAl+fulvestrantAl+palbociclib,Laterelapse(12monthssinceadjuvanttherapy),Earlyrelapse(12monthssinceadjuvanttherapy),Laterelapse(12monthssinceadjuvanttherapy),Earlyrelapse(12monthssinceadjuvanttherapy),PriortreatmentwithanAlandOFS,PriortreatmentwithtamoxifenwithorwithoutOFS,Prioradjuvantendocrinetherapy,Noprioradjuvantendocrinetherapy,OFS,二线治疗方案的选择,一线方案和DFI会影响二线药物选择,目前，对辅助治疗耐药缺乏明确、可靠的定义。也没有证据以辅助治疗为基础指导一线，二线的选择。,若病人分期较早而DFI短，或者在辅助内分泌治疗时就发生进展，后续的内分泌治疗效果可能较差。,一线方案和DFI对二线方案的影响,500mg/IMonDays0,14,and18,followedby500mgevery28days,500mg/IMonday0,250mgondays14and28,then250mgevery28days,Fulvestrant的使用方式,JNatlCancerInst106:djt337,2014,绝经后乳腺癌二线用哪种药物？,Al(nonsteroidal)FulvestrantAl+palbociclibTamoxifen,FulvestrantpalbociclibAl+everolimusAl(steroidal)Tamoxifen,Al(nonsteroidal)Al+fulvestrantAl+palbociclibTamoxifen,Al(nonsteroidal)FulvestrantAl+palbociclib,Al,nonsteroidalpreferredAl+fulvestrantAl+palbociclib,Firstline,FulvestrantpalbociclibAl+everolimusAl(steroidal)Tamoxifen,FulvestrantpalbociclibAl+everolimusAl(steroidal)Tamoxifen(laterelapse),Dependingonpriortherapy:FulvestrantpalbociclibAl+everolimusAl(steroidal)Tamoxifen,Sequentialtherapybasedonpriorexposureandresponsetohormonetherapy,Al(nonsteroidal)FulvestrantAl+palbociclibTamoxifen,FulvestrantpalbociclibAl+everolimusAl(steroidal)Tamoxifen,Al(nonsteroidal)Al+fulvestrantAl+palbociclibTamoxifen,Al(nonsteroidal)FulvestrantAl+palbociclib,Al,nonsteroidalpreferredAl+fulvestrantAl+palbociclib,OFS,绝经前乳腺癌二线用哪种药物？,FulvestrantpalbociclibAl+everolimusAl(steroidal)Tamoxifen,FulvestrantpalbociclibAl+everolimusAl(steroidal)Tamoxifen(laterelapse),Dependingonpriortherapy:FulvestrantpalbociclibAl+everolimusAl(steroidal)Tamoxifen,Firstline,Secondline(withContinuedOFS),Sequentialtherapybasedonpriorexposureandresponsetohormon