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1、2013 ASCO 乳腺癌内分泌治疗进展,广州中山大学肿瘤医院 内科 刘冬耕 2013-07-6 湛江,内容,辅助内分泌治疗(延长治疗改善疗效) aTTom ATLAS MA-17 晚期乳腺癌治疗进展(乳腺癌耐药研究进展) BOLERO 2 TANDEM EGF 其他新药 其他研究(包括基础和临床),Recurrences,Breast Cancer Deaths,超过半数乳腺癌的复发和死亡出现在 他莫昔芬结束后,Adapted with permission. Early Breast Cancer Trialists Collaborative Group Meeting, 2000.,Y
2、ears,85.2,76.1,68.2,73.7,62.7,54.9,68%,55%,0,20,40,60,80,100,0,5,10,15,Tamoxifen Control,15%,17%,0,20,40,60,80,100,0,5,10,15,73%,64%,80.9,73.0,87.8,73.2,64.0,Years,Tamoxifen Control,9%,18%,91.4,% of patients,% of patients,20,187 women with ER-positive or ER-unknown disease randomised in 5 trials of
3、10 vs 5 years of tamoxifen:,ECOG, Scottish& NSABP B-14 1,588 ATLAS* 11,646 aTTom 6,953 ALL TRIALS 20,187,* ATLAS, Lancet 2013; 381: 805-16,aTTom: Long-term effects of continuing adjuvant tamoxifen to 10 years versus stopping at 5 years in 6,953 women with early breast cancer,Richard Gray,Daniel Rea,
4、Kelly Handley& 17 others on behalf of the aTTom Collaborators,5 years of tamoxifen versus no tamoxifen*,10 vs 5 years of tamoxifen: effect on breast cancer recurrence,ASCO 2013,复发率分别为:28%和32%,p=0.003,10 vs 5 years of tamoxifen: Recurrence by year of follow-up,10 vs 5 years of tamoxifen: Breast Cance
5、r Death by Treatment Allocation,10 vs 5 years of tamoxifen: Death after recurrence by year of follow-up,10 vs 5 years of tamoxifen: Death Without Recurrence by Treatment,10 vs 5 years of tamoxifen: All cause mortality by treatment,10 vs 5 years of tamoxifen: Overall survival by treatment and year of
6、 follow-up,10 vs 5 years of tamoxifen: Overall survival by treatment and year of follow-up,Main risk: endometrial cancers: absolute hazard 0.5%,ATLAS: 6846 women, ER+, 10 vs 5 years tamoxifen,ATLAS, Lancet 2013;381 805-16,10 yrs vs 5 yrs BREAST CANCER MORTALITY IN ER+ rate ratio* by period in aTTom
7、and ATLAS,p=0.007 #p=0.002 p=0.00004 p=0.1 p=0.004 p=0.001,*Inverse-variance-weighted estimate of the effect in ER+(ATLAS, Lancet 2013),ER+ 10 yrs vs 5 yrs OVERALL SURVIVAL rate ratio* by period in aTTom and ATLAS,p=0.0007 p=0.008,*Inverse-variance-weighted estimate of the effect in ER+(ATLAS, Lance
8、t 2013),Conclusions,aTTom and ATLAS together provide proof beyond reasonable doubt that continuing tamoxifen beyond 5 years reduces recurrence over the following years: no effect in years 5-6, benefit mainly after year 7 Continuing tamoxifen beyond 5 years also reduces breast cancer mortality: no ef
9、fect in years 5-6 ,25% reduction after year 10. 10 years tamoxifen vs no tamoxifen reduces breast cancer mortality by a third in the first decade and a half in the second decade,ATLAS:10 years of tamoxifen vs 5: (Adjuvant Tamoxifen - Longer Against Shorter),6846 women with ER+ disease completed 5yea
10、rs of tamoxifen, then were randomised to: CONTINUE to year 10, or STOP at year 5 54% node-negative 8 yrs follow-up: compliance, recurrence, death,SABCS 2012,Results:,Recurrence: 617 vs 711 women (2p=0.002) Breast cancer mortality: 331 vs 397 (2p=0.01) Overall mortality: 639 vs 722 (2p=0.01) Recurren
11、ce and breast cancer mortality Little effect during years 5-9 benefit mainly after year 10,ATLAS:10 years of tamoxifen vs 5:,ER+:他莫昔芬10年 vs. 5年治疗对 副反应与乳腺癌死亡率的作用,Davis C, et al. 2012 SABCS Abstract S1-2.,*EBCTCG. Lancet 2011; 378:771-784. ATLAS=Adjuvant Tamoxifen - Longer Against Shorter,估计10年他莫昔芬 vs
12、. 0的15年死亡率:绝对获益是绝对损失的30倍,绝经后HR阳性EBC,延长辅助内分泌治疗 MA.17 试验设计,Primary end point: DFS Secondary end points: OS/safety/QOL Substudies: BMD/bone markers, lipid profile,*n=2575 (efficacy), 2154 (safety); n=2582 (efficacy), 2145 (safety). QOL = quality of life; BMD = bone mineral density.,Goss et al. N Engl J
13、 Med. 2003;349:1793.,N=5187, MF2.4 year,DFS and OS,首次分析事件数207,中位随访2.4年。 预计4年无复发生存分别为93%和87%(p0.001) 两组死亡分别为42 vs 31(p=0.25),OS没有区别。 但是来曲唑组轻度潮热,骨关节,肌肉疼痛常见,阴道出血少见。 新发骨质疏松5.8和4.5(p=0.07),来曲唑稍高。,Goss et al. N Engl J Med. 2003;349:1793.,延长辅助内分泌治疗: Letrozole After 5 Years of Tamoxifen,A similar reduction
14、in local recurrences, new primaries, and distant recurrences occurred in node-positive and node-negative patients,Goss PE, et al. SABCS 2005. Abstract 16.,Goss PE, et al. SABCS 2005. Abstract 16.,Letrozole After Unblinding of MA.17,Goss PE, et al. SABCS 2005. Abstract 16.,DFS,Distant DFS,OS,Contrala
15、teral breast cancer,HR,0.31,0.28,0.53,0.23,0,0.1,0.2,0.3,0.4,0.5,0.6,PLAC-LET to PLAC,P .0001,P .002,P .05,P .012,来曲唑 疗效明显优于安慰剂( MA.17 ),The hazard ratios (HRs) of letrozole and placebo from the IPCW analyses(MA17),median follow-up(first interim analysis) 2.5 years. more than 60% of placebo patients crossed over to letrozole after being unblinded Now median follow-up 64 months HR 0.52 (95% CI, 0.45 to 0.61; P .001) for DFS, HR 0.51 (95% CI, 0.42to 0.61; P .001) for distant disease-free survival (DDFS) HR 0.61 (95% CI, 0.52 to 0.71;P .001) for overall s