乳腺癌内科治疗新进展—— 胡夕春

Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,乳腺癌内科治疗新进展,胡夕春,新药新方案 新理念 新药不良反响及处理,1.1白蛋白结合紫杉醇(ABX),ORR,PFS,ABX 300 mg/m2,Q3W,33,ABX 100mg/m2,QW3,58,ABX 150 mg/m2,QW3,62,多西他赛100 mg/m2,Q3W,36,1.2 EFECT:Evaluation of Treatment Options Following AI Failure,Fulvestrant,IM injection,loading-dose regimen*(n=351),Exemestane,25 mg/day orally,(n=342),Postmenopausal women with hormone receptorpositive,progressing/recurring,advanced breast cancer,after nonsteroidal AI,(N=693),Progression,death,or withdrawal,*Fulvestrant loading-dose regimen comprised,500 mg on Day 0,250 mg on Days 14 and 28,and 250 mg monthly thereafter.,Gradishar W,et al.SABCS 2006.Abstract 12.,EFECT:,Similar,TTP in Patients Treated With Fulvestrant or Exemestane,Gradishar W,et al.SABCS 2006.Abstract 12.,0,0.0,0.2,0.4,0.6,0.8,1.0,342,190,98,41,21,12,8,6,1,Proportion of Patients,Progression Free,Months,No.at Risk,Fulvestrant,Exemestane,3,6,9,12,15,18,21,24,27,351,195,96,50,25,12,4,2,0,0,0,Exemestane,Fulvestrant,EFECT:Patient Response and Study Conclusions,Median duration of response to treatment with fulvestrant vs exemestane:13.5 vs 9.8 months,respectively,Fulvestrant as effective and safe as exemestane in women with hormone receptorpositive breast cancer who have progressed on treatment with a nonsteroidal AI,Outcome,%,Exemestane(n=342),Fulvestrant(n=351),Odds Ratio(95%CI),P,Value,ORR,6.7,7.4,1.120(0.578-2.186),.7364,CBR,31.5,32.2,1.035(0.720-1.487),.8534,Gradishar W,et al.SABCS 2006.Abstract 12.,Anthracyclin,-pretreated,and taxane resistant,N:752,R,A,N,D,O,M,I,Z,C,I,Ixabepilone,40 mg/m,2,d 1 静脉滴注3h,Capecitabine,1000 mg/m,2,po.,BID,x 14,Capecitabine,1250 mg/m,2,po.,BID x,14,1.3,Ixabepilone+Capecitabine,vs Capecitabine,L.T.Vahdat et al.Proc ASCO 2007.Abstr 1006,Ixabepilone+Capecitabine vs Capecitabine,L.T.Vahdat et al.Proc ASCO 2007.Abstr 1006,Ixabepilone+Capecitabine vs Capecitabine,L.T.Vahdat et al.Proc ASCO 2007.Abstr 1006,新药新方案 新理念 新药不良反响及处理,2.1,Lapatinib oral tyrosine kinase inhibitor of ErbB1 and ErbB2,Blocks signaling through EGFR and HER2 homodimers and heterodimers,May also prevent signaling between ErbB1/ErbB2 and other ErbB family members,PTEN,Lapatinib,P13K,pAkt,Ras,Raf,pErk,Shc,Grb2,So8,Phospholipid cell membrane,Treatment Efficacy:Lapatinib Vs Lapatinib+Trastuzumab,*Confirmed CR+PR,CR+PR+SD 6 mo,Clinical Response,LN=145,L+TN=146,Response Rate,%*(95%CI),6.9(3.4,12.3),10.3(5.9,16.4),Odds Ratio(95%CI),1.5(0.6,3.9)p=0.46,Clinical Benefit Rate,%,(95%CI),12.4(7.5,18.9),24.7(17.9,32.5),Odds Ratio(95%CI),2.2(1.2,4.5)p=0.01,OShaughnessy J,et al.ASCO 2021.Abstract 1015.,Progression-Free Survival:L Vs L+T,L,N=145,L+T,N=146,Progressed or Died,n,128,127,Median,wks,8.1,12.0,Hazard ratio(95%CI),0.73(0.57,0.93),P,value,.008,Subjects At Risk,148,148,L,L+T,53,73,21,42,13,27,5,8,0,2,6 Mo PFS,Cumulative%Alive Without Progression,13%,28%,0,20,40,60,80,100,0,10,20,30,40,50,60,Time from Randomization(wks),OShaughnessy J,et al.ASCO 2021.Abstract 1015.,Geyer CE,et al.ASCO 2006.Clinical Science Symposium.,EGF100151:Lapatinib+Capecitabine in Advanced Breast Cancer,Refractory,progressive metastatic or locally advanced HER2+breast cancer previously treated with anthracycline,taxane,or trastuzumab,(N=528 planned*),Lapatinib,1250 mg daily+,Capecitabine,2000 mg/m,2,dailyfor Days 1-14,3-week cycles(n=160),Capecitabine,2500 mg/m,2,dailyfor Days 1-14,3-week cycles(n=161),Follow-up:until progressionor unacceptabletoxicity,*Study enrollment terminated early by IDMC due to superiority of combination arm in primary endpoint.,EGF100151:Lapatinib+Capecitabine in Advanced Breast Cancer(contd),Addition of lapatinib to capecitabine in women with treatment-refractory,advanced metastatic breast cancer associated with,Longer time to progression,36.9 vs 19.7 wks(,P,=.00016),Longer progression-free survival,36.9 vs 17.9 wks(,P,=.000045),Fewer progressions or deaths,38%vs 48%,Response(independent review),Overall:22.5%vs 14.3%(,P,=.113),Geyer CE,et al.ASCO 2006.Clinical Science Symposium.,Progression-Free Survival(%),Time(Wks),20,40,60,80,0,100,10,20,30,40,50,Capecitabine,Lapatinib+capecitabine,ITT population,Docetaxel+Avastin,15mg/kg every3 weeks,Phase III trial of Avastin plus docetaxel in first-line MBC(AVADO),Recruitment commenced March 2006 and completed in March 2007,Primary endpoint:PFS,secondary endpoints:ORR,OS,safety,QoL,Trial met primary endpoint;data will be presented mid-2021,Previously untreated HER2-negative locally recurrent or MBC(n=705),Docetaxel 100mg/m,2,every 3 weeks+placebo,Docetaxel+Avastin,7.5mg/kg every3 weeks,PI:David Miles,Treat to disease progression,Treat to disease progression,Treat to disease progression,R,HR+95%CI(unstratified),Bev 7.5,+Docetaxel(n=248),Mos,AVADO Trial Progression-Free Survival:By Bevacizumab Dose,*Data censored for non-protocol therapy prior to PD,mg/kg Q3W