晚期HR+ HER2-乳腺癌内分泌治疗的几点思考

1、,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？TAM or AI?,12个月 or 12个月？,Pre or Peri or Post？,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

2、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.Cochrane Database Syst Rev. 2009 Oct 7;(4):CD003370. 2. Lancet. 2016 Dec 17;388(10063):2997-3005 3. Cochrane Database Syst Rev. 2012 Jul 11;(7):CD008926. 4. Lancet Oncol. 2015 Jan;16(1):25-35.,相关证据,BOLERO-2的结果支持

3、依维莫司+依西美坦应用于一线内分泌治疗（Progressed within 12 mo or on nonsteroidal AI, or any time on tamoxifen) 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.N Engl J Med. 2012 Feb 9;366(6):520-9. 2. Lancet Oncol. 2016 Apr;17(4):425-39.3.,用哪种药物？,Al (nonsteroidal) Fulvestrant Al + palbociclib Tamoxifen,Fulvestrant palbociclib

4、Al + everolimus Al (steroidal) Tamoxifen,Al (nonsteroidal) Al + fulvestrant Al + palbociclib Tamoxifen,Al (nonsteroidal) Fulvestrant Al + palbociclib,Al, nonsteroidal preferred Al + fulvestrant Al + palbociclib,Late relapse ( 12 months since adjuvant therapy),Early relapse ( 12 months since adjuvant

5、 therapy),Late relapse ( 12 months since adjuvant therapy),Early relapse ( 12 months since adjuvant therapy),Prior treatment with an Al,Prior treatment with tamoxifen,Prior adjuvant endocrine therapy,No prior adjuvant endocrine therapy,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

6、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.J Clin Oncol. 2016 Sep 1;34(25

7、):3069-103. 2.Ann Oncol. 2017 Jan 1;28(1):16-33.,用哪种药物？,Al (nonsteroidal) Fulvestrant Al + palbociclib Tamoxifen,Fulvestrant palbociclib Al + everolimus Al (steroidal) Tamoxifen,Al (nonsteroidal) Al + fulvestrant Al + palbociclib Tamoxifen,Al (nonsteroidal) Fulvestrant Al + palbociclib,Al, nonsteroi

8、dal preferred Al + fulvestrant Al + palbociclib,Late relapse ( 12 months since adjuvant therapy),Early relapse ( 12 months since adjuvant therapy),Late relapse ( 12 months since adjuvant therapy),Early relapse ( 12 months since adjuvant therapy),Prior treatment with an Al and OFS,Prior treatment wit

9、h tamoxifen with or without OFS,Prior adjuvant endocrine therapy,No prior adjuvant endocrine therapy,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,500 mg/IM on Days 0, 14, and 18, followed by 500 mg ever

10、y 28 days,500 mg/IM on day 0, 250 mg on days 14 and 28, then 250 mg every 28 days,Fulvestrant的使用方式,J Natl Cancer Inst 106:djt337, 2014,绝经后乳腺癌二线用哪种药物？,Al (nonsteroidal) Fulvestrant Al + palbociclib Tamoxifen,Fulvestrant palbociclib Al + everolimus Al (steroidal) Tamoxifen,Al (nonsteroidal) Al + fulve

11、strant Al + palbociclib Tamoxifen,Al (nonsteroidal) Fulvestrant Al + palbociclib,Al, nonsteroidal preferred Al + fulvestrant Al + palbociclib,First line,Fulvestrant palbociclib Al + everolimus Al (steroidal) Tamoxifen,Fulvestrant palbociclib Al + everolimus Al (steroidal) Tamoxifen (late relapse),De

12、pending on prior therapy: Fulvestrant palbociclib Al + everolimus Al (steroidal) Tamoxifen,Sequential therapy based on prior exposure and response to hormone therapy,Al (nonsteroidal) Fulvestrant Al + palbociclib Tamoxifen,Fulvestrant palbociclib Al + everolimus Al (steroidal) Tamoxifen,Al (nonstero

13、idal) Al + fulvestrant Al + palbociclib Tamoxifen,Al (nonsteroidal) Fulvestrant Al + palbociclib,Al, nonsteroidal preferred Al + fulvestrant Al + palbociclib,OFS,绝经前乳腺癌二线用哪种药物？,Fulvestrant palbociclib Al + everolimus Al (steroidal) Tamoxifen,Fulvestrant palbociclib Al + everolimus Al (steroidal) Tamoxifen (late relapse),Depending on prior therapy: Fulvestrant palbociclib Al + everolimus Al (steroidal) Tamoxifen,First line,Second line(with Continued OFS),Sequenti