乳腺癌的新辅助治疗课件.ppt

1、.OPEN ISSUES IN MULTIDISCIPLINARY BREAST CANCER MANAGEMENTMediterranean School of OncologyRome,March 30,2012NEOADJUVANT THERAPYLucia MentucciaOncologia Medica,Sora.To improve surgical outcomes and options-For operable breast cancer,the aim is to increase the chance of breast conserving surgery in pa

2、tients who would otherwise require mastectomy-For inoperable locally advanced breast cancers,the aim is to achieve operability To gain information on tumor response To define short-term surrogate markers of response Goals of Neoadjuvant Theapy in Breast Cancer.1523 pts with clinical T1-3,N0-N1 breas

3、t cancer Stratification Age Clinical Tumor Size Clinical Nodal StatusOperationOperationNSABP B-18Wolmark N t al;J Natl Cancer Inst Monogr.2001AC x 4AC x 4.36%20%43%cCR(249 pts)cPR(296 pts)cSD+cPD(140 pts)23%4%9%pInv(160 pts)pNon-Inv(26 pts)pCR(63 pts)NSABP B-18:Clinical and Pathologic Breast Tumor R

4、esponseWolmark N t al;J Natl Cancer Inst Monogr.2001.NSABP B-18:Surgery Performed100806040200%P 5 cm ER or PgR+vs.ER&PgR N 0-1 vs.N 2 Conservative surgery or notInvasive operableHER2+BCT 2 cm(inflammatory BC excluded)LVEF 50%N=450 34 weeks52 weeks of anti-HER2 therapylapatinibtrastuzumablapatinibtra

5、stuzumabFEC X3SURGERYRANDOMIZElapatinib trastuzumablapatinibtrastuzumabpaclitaxel paclitaxel paclitaxel+12 wks6 wks.Efficacy pCR and tpCR39Efficacy Overall(Clinical)Responseat 6 weeks(w/o chemo)and at surgeryL:lapatinib;T:trastuzumab;L+T:lapatinib plus trastuzumab.Safety No major cardiac dysfunction

6、 One death in L+T immediately after end of treatmentL(N=154)T(N=149)L+T(N=152)Diarrhea36(23%)3(2%)32(21%)Hepatic*20(13%)2(1%)13(9%)Neutropenia24(16%)4(3%)13(9%)Skin disorders10(7%)4(3%)10(7%)Number(%)of patients with AEs at Grade 3 L:lapatinib;T:trastuzumab;L+T:lapatinib plus trastuzumab*Includes 2

7、patients with Hys Law criteria in T,and one patient in L.RANDOMIZATIONLapatinib 1000 mg/dailyLapatinib 1500 mg/dailyCOREBIOPSY SURGERY ChemotherapyABCTXL 80 mg/m2Trastuzumab 2 mg/kg5 FU 600 mg/m2Epi 75 mg/m2CTX 600 mg/m2CHER LOB Trial:study planGuarneri V,ASCO 2011121 paz.pCR (breast&axilla)Node neg

8、ativityBreast conservation0102030405060708090Arm A:CT+trastuzumabArm B:CT+lapatinibArm C:CT+trastuzumab/lapatinibCHER-LOB:EFFICACY OUTCOMESGuarneri V,ASCO 2011.NeoSphere:study designTHP(n=107)docetaxel+trastuzumab+pertuzumab HP(n=107)trastuzumab+pertuzumab TP(n=96)docetaxel+pertuzumab SURGERYdocetax

9、el q3w x 4FEC q3w x 3 trastuzumab q3w cycles 517FEC q3w x 3trastuzumab q3w cycles 517FEC q3w x 3trastuzumab q3w cycles 517FEC q3w x 3trastuzumab q3w cycles 521Study dosing:q3w x 4TH(n=107)docetaxel+trastuzumab Patients with operable or locally advanced/inflammatory*HER2-positive BC Chemo-nave&primar

10、y tumors 2cm(N=417)BC,breast cancer;FEC,5-fluorouracil,epirubicin and cyclophosphamide*Locally advanced=T23,N23,M0 or T4ac,any N,M0;operable=T23,N01,M0;inflammatory=T4d,any N,M0H,trastuzumab;P,pertuzumab;T,docetaxelGianni L et al.SABCS 2010.H,trastuzumab;P,pertuzumab;T,docetaxelNeoSphere pCR rates:I

11、TT population summaryp=0.014150403020100THTHPHPTPpCR,%95%CIp=0.00329.045.816.824.06Gianni L et al.SABCS 2010.010203040506070THTHPHPTPER or PR posER and PR neg20.026.017.436.829.130.063.25.9pCR,%95%CIH,trastuzumab;P,pertuzumab;T,docetaxelGianni L et al.SABCS 2010NEOSPHERE:pCR and hormone receptors st

12、atus.L:lapatinib;T:trastuzumab;L+T:lapatinib plus trastuzumabpCR pathologic complete response HR:hormone receptors pCR by hormone receptor statusBaselga J et al.SABCS 2010.T:trastuzumab;L:lapatinib;T+L:trastuzumab plus lapatinibCHER-LOB:pCR rate by HR25%22.7%0102030405060Arm A(CT+T)Arm B(CT+L)Arm C(

13、CT+T+L)26.6%35.7%56.2%35.7%HR+HR+HR+HR-HR-HR-.Trial/author pts#RegimenHR+%pCRHR-HR+Kemeny54FACVb6620.07.7Ring435CMF,A/E7121.68.1Bear1211AC5913.65.7Bear565AC+T5722.814.1GEPARDO250ddAD+/-T5615.41.1GEPARDUO913ddAD/CA-D7422.86.2GEPARTRIO286TAC/TAC-NX6836.610.1Guarneri1731FAC+/-P6823.87.8Gianni438A+/P/CM

14、F6342.211.6Guarneri201FEC/ET/GET7416.63.5Colleoni399ECF/EC/ET/ViFuP6833.37.6HORMONE RECEPTOR STATUS AND pCR.Neoadjuvant therapy in HER2+operable breast cancer:Key FindingsPatient selection is mandatory for the integration of novel agents in cancer treatment Chemotherapy+trastuzumab is the gold stand

15、ardDouble-HER2 blockade increases the pCR rateEndocrine pathway is still important even in presence of HER2 co-expressionThe preoperative setting is ideal to test new combinations through the“window of opportunity model”.Should neoadjuvant regimens for HER2-positive disease always contain anti-HER2

16、drug?Yes No A Is dual HER2-targeting a reasonable option for the preoperative setting for HER2 disease?Yes No A8.5%87.2%4.3%67.4%21.7%10.9%Neo Adjuvant Systemic TherapySt Gallen 2011.Von Minckwitz G,SABCS 2010.Von Minckwitz G,SABCS 2010.Von Minckwitz G,SABCS 2010.OBJECTIVESVon Minckwitz G,SABCS 2010

17、.Von Minckwitz G,SABCS 2010.CHARACTERISTICS OF PATIENTS.Von Minckwitz G,SABCS 2010.Neoadjuvant Bevacizumab and Anthracycline-Taxane Based Chemotherapy in 684 Triple Negative Primary Breast Cancers:Secondary Endpoint Analysis of the GEPARQUINTO Study(GBG 44)Gerber B et al.Proc ASCO 2011;Abstract 1006

18、.Gerber B et al.Proc ASCO 2011;Abstract 1006.Gerber B et al.Proc ASCO 2011;Abstract 1006.GEPARQUINTO:Benefit of Bevacizumab Added to Neoadjuvant Chemotherapy in TNBC SubgroupGerber B et al.Proc ASCO 2011;Abstract 1006.Benefit of bev limited to TNBC subgroup pCRbreast(with bev vs without bev)*TNBC pa

19、tients:36.4 vs 27.8%(p=0.021)All patients:15.0 vs 17.5%(p=NS)*pCRbreast=no inv/non-inv in breast and nodesGerber B et al.Proc ASCO 2011;Abstract 1006.The Effect of pCR of Bevacizumab and/or Antimetabolites Added to Standard Neoadjuvant Chemotherapy:NSABP Protocol B-40Bear HD et al.Proc ASCO 2011;Abs

20、tract LBA1005.Bear HD et al.Proc ASCO 2011;Abstract LBA1005.NSABP B-40:Chemotherapy Bevacizumab in Patients with Operable HER2-Negative Breast CancerOperableBreastCancerRTissue forBiomarkersSURGERYTissue forBiomarkers+/-+/-X10T docetaxelX capecitabine G gemcitabine B bevacizumab.NSABP B-40:Benefit o

21、f Adding Bevacizumab to Standard ChemotherapyBear HD et al.Proc ASCO 2011;Abstract LBA1005.Benefit of bev predominant in HR+and not TNBC patient subgroup pCRbreast(with bev vs without bev):HR+patients:23.3 vs 15.2%(p=0.008)TNBC patients:51.3 vs 47.3%(p=0.44).Yes No A If YES,for which duration(choose one)?2.2%97.8%0%Neo Adjuvant Systemic Therapy Is neodjuvant endocrine therapy alone a reasonable option for postmenopausal pts with highly endocrine-responsive disease?-3-4 months -4-8 months-Maximal response15.2%39.1%45.7%St Gallen 2011.Grazie!