《乳腺癌内科治疗新进展—— 胡夕春》由会员分享，可在线阅读，更多相关《乳腺癌内科治疗新进展—— 胡夕春（46页珍藏版）》请在金锄头文库上搜索。
1、复旦大学附属肿瘤医院乳腺癌内科治疗新进展胡夕春新药 新方案 新理念 新药不良反应及处理 1.1白蛋白结合紫杉醇 (ABX) ORRPFSABX 300 mg/m2,Q 3W 33ABX 100mg/m 2,QW3 58ABX 150 mg/m2, QW3 62多西他赛 100 mg/m2,Q 3W 361.2 EFECT: Evaluation of Treatment Options Following AI FailureFulvestrantIM injection loading-dose regimen* (n = 351)Exemestane 25 mg/day orally (n
2、 = 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
3、al. SABCS 2006. Abstract 12.EFECT: Similar TTP in Patients Treated With Fulvestrant or ExemestaneGradishar W, et al. SABCS 2006. Abstract 12.00.00.20.40.60.81.034219098412112861Proportion of Patients Progression Free MonthsNo. at Risk Fulvestrant Exemestane369121518212427351195965025124200 0Exemesta
4、neFulvestrantEFECT: 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 w
5、ith a nonsteroidal AIOutcome, %Exemestane (n = 342)Fulvestrant (n = 351)Odds Ratio (95% CI)P ValueORR6.77.41.120 (0.578-2.186).7364CBR31.532.21.035 (0.720-1.487).8534Gradishar W, et al. SABCS 2006. Abstract 12.Anthracyclin -pretreated and taxane resistantN: 752R A N D O M I Z C I Ixabepilone40 mg/m2
6、 d 1 静脉滴注3h Capecitabine 1000 mg/m2 po. BID x 14Capecitabine 1250 mg/m2 po. BID x 141.3 Ixabepilone+Capecitabinevs CapecitabineL.T. Vahdat et al. Proc ASCO 2007. Abstr 1006Ixabepilone+Capecitabine vs CapecitabineL.T. Vahdat et al. Proc ASCO 2007. Abstr 1006Ixabepilone+Capecitabine vs CapecitabineL.T
7、. Vahdat et al. Proc ASCO 2007. Abstr 1006新药 新方案 新理念 新药不良反应及处理 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 membersPTENLapatinibP13KpAktRasRafpEr
8、kShc Grb2So8Phospholipid cell membraneTreatment Efficacy: Lapatinib Vs Lapatinib + Trastuzumab*Confirmed CR+PR CR+PR+SD 6 mo Clinical Response L N=145L + T N=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
9、(7.5, 18.9)24.7 (17.9, 32.5) Odds Ratio (95% CI) 2.2 (1.2, 4.5) p=0.01OShaughnessy J, et al. ASCO 2008. Abstract 1015.Progression-Free Survival: L Vs L+TL N = 145L+T N = 146Progressed or Died, n128127 Median, wks8.112.0 Hazard ratio (95% CI)0.73 (0.57, 0.93) P value.008Subjects At Risk 148 148L L+T5
10、3 7321 4213 275 80 26 Mo PFSCumulative % Alive Without Progression13%28%0204060801000102030405060Time from Randomization (wks)OShaughnessy J, et al. ASCO 2008. Abstract 1015.Geyer CE, et al. ASCO 2006. Clinical Science Symposium.EGF100151: Lapatinib + Capecitabine in Advanced Breast CancerRefractory
11、, 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/m2 daily for Days 1-14, 3-week cycles (n = 160)Capecitabine 2500 mg/m2 daily for Days 1-14, 3-week cycles (n
12、= 161)Follow-up: until progression or unacceptable toxicity*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-refracto
13、ry, advanced metastatic breast cancer associated with Longer time to progression36.9 vs 19.7 wks (P = .00016) Longer progression-free survival36.9 vs 17.9 wks (P = .000045) Fewer progressions or deaths38% vs 48% Response (independent review)Overall: 22.5% vs 14.3% (P = .113)Geyer CE, et al. ASCO 200
14、6. Clinical Science Symposium.Progression-Free Survival (%)Time (Wks)2040608001001020304050CapecitabineLapatinib + capecitabineITT populationDocetaxel + Avastin 15mg/kg every 3 weeksPhase III trial of Avastin plus docetaxel in first- line MBC (AVADO)lRecruitment commenced March 2006 and completed in
15、 March 2007lPrimary endpoint: PFS secondary endpoints: ORR, OS, safety, QoLlTrial met primary endpoint; data will be presented mid-2008Previously untreated HER2-negative locally recurrent or MBC (n=705)Docetaxel 100mg/m2 every 3 weeks + placeboDocetaxel + Avastin 7.5mg/kg every 3 weeksPI: David Mile
16、sTreat to disease progressionTreat to disease progressionTreat to disease progressionRHR + 95% CI (unstratified)Bev 7.5 +Docetaxel (n = 248)MosAVADO Trial Progression-Free Survival: By Bevacizumab Dose*Data censored for non-protocol therapy prior to PD mg/kg Q3WHR + 95% CI (stratified*).69 (.54.89) P = .0035.79 (.63.98) P = .0318Placebo
