Presentation on theme: "CLINICAL CASE Highlights in the Management of Breast Cancer"— Presentation transcript:
1CLINICAL CASE Highlights in the Management of Breast Cancer Rome, May 25-26, 2007CLINICAL CASEDott.ssa Jamara GiampietroCattedra di Oncologia MedicaUniversità “G. D’Annunzio” Chieti-PescaraDirettore: Prof. Stefano Iacobelli
2Core needle biopsy: ductal infiltrating carcinoma, G3 69 years old, femaleComorbility: hypertension and osteoporosisDecember 2006: mammogram and breast ultrasound showed a 4.3 cm massCore needle biopsy: ductal infiltrating carcinoma, G3ER=80% PR=10% HER2+++Chest immaging Bone scan negativeAbdominal ultrasoundEchocardiogram LVEF:55%
3The best therapeutic approach? primary systemic therapyimmediate surgery
4Randomized phase III trials comparing neoadjuvant with adjuvant therapy using the same chemotherapy regimenSachelarie et al, The Oncologist 2006;11:The goals of PST in breast cancer are to treat occult systemic disease, decrease the tumor bulk (optimally to a complete pathologic response), and reduce the extent of local surgery to allow breast-conserving surgery.
9The best therapeutic approach? Anthracycline-based chemoterapyTaxane-based chemoterapyAnthracycline-taxane-basedchemoterapyTrastuzumab?
10Randomized trials comparing different neoadjuvant chemotherapy regimenSachelarie et al, The Oncologist 2006;11:The sequential use of an anthracycline with a taxane is associated with better results than their concurrent use. However, it is impossible to determine whether the observed benefit is a result of the sequential use or because of differences in total delivered dose of chemotherapy(higher in the sequential arm) or treatment duration ( longer in the sequential arm).
11[ 4 P* + 4 FE(75)C ] + H weekly Clinical stage II and IIIa HER2 FISH 3+or HIC +4 P* + 4 FE(75)C[ 4 P* + 4 FE(75)C ] + H weekly* Paclitazel was administered at 225 mg/mq as a 24-hours continuous infusion.The primary objective of the study was to compare pCR rate between the two arms.
13BCIRG 006 ACT ACTH TCH 4 x AC 60/600 mg/m2 4 x Docetaxel Her 2+ (Central FISH)N+or highrisk N-4 x AC 60/600 mg/m24 x Docetaxel100 mg/m2ACTH1 Year Trastuzumab6 x Docetaxel and Carboplatin75 mg/m2 AUC 6N=3,222TCHStratified by Nodes and Hormonal Receptor Status1 Year TrastuzumabSlamon D., SABCS 2006
15Disease Free Survival 2nd Interim Analysis Absolute DFS benefits(from years 2 to 4):ACTH vs ACT: 6%TCH vs ACT: 5%1.093%0.992%87%83%86%87%0.882%81%% Disease Free77%0.7PatientsEvents1073192AC->T0.61074128AC->THHR (AC->TH vs AC->T) = 0.61 [0.48;0.76] P<0.00011075142TCHHR (TCH vs AC->T) = 0.67 [0.54;0.83] P=0.00030.512345Year from randomizationSlamon D., SABCS 2006
16Overall Survival 2nd Interim Analysis 1.099%97%98%97%95%92%93%0.991%86%% Survival0.80.7PatientsEvents0.6107380AC->T107449AC->THHR (AC->TH vs AC->T) = 0.59 [0.42;0.85] P=0.004107556TCHHR (TCH vs AC->T) = 0.66 [0.47;0.93] P=0.0170.512345Year from randomizationSlamon D., SABCS 2006
17DFS Lymph Node Negative 2nd Interim Analysis 1.099%95%97%94%94%93%0.992%88%86%0.8% Disease Free0.7PatientsEvents0.630935AC->T31012AC->THHR (AC->TH vs AC->T) = 0.32 [0.17;0.62] P=0.000730917TCHHR (TCH vs AC->T) = 0.47 [0.26;0.83] P=0.00960.512345Year from randomizationSlamon D., SABCS 2006
18Overall Survival Lymph - Node Negative 2nd Interim Analysis 100%100%1.098%99%98%97%98%96%93%0.9% Survival0.80.7PatientsEvents30712AC->T0.63092AC->THHR (AC->TH vs AC->T) = 0.16 [0.04;0.73] P=0.0183075TCHHR (TCH vs AC->T) = 0.42 [0.15;1.2] P=0.1060.512345Year from randomizationSlamon D., SABCS 2006
19DFS - Subpopulations AC-TH vs AC-T TCH vs AC-T AC-TH better AC-T 1.00.02.0AC-THbetterAC-TSubgroupNode negNode posHR -HR +Tsize <2cmTsize ≥2cmAC-TH vs AC-T1.00.02.0SubgroupNode negNode posHR -HR +Tsize <2cmTsize ≥2cmTCH vs AC-TTCHbetterAC-T
20Cardiac Deaths and CHF as per Independent Review Panel AC-Tn=1,050AC-THn=1,068TCHn=1,056Cardiac related deathCardiac left ventricular function (CHF)Grade 3 / 43174second interim analysis/ 0/ 4/ 20P =first interim analysisData from follow_time.sasSummary Statistics for Time: rando_lastfup_cens_monSlamon D., SABCS 2006
21Patients with >10% relative LVEF decline AC-Tn = 1012AC-THn = 1040TCHn = 1029Patients9118082%917.38P <0.0001P = 0.5second interim analysis/102/189/89/10/18/8.6/1014/1042/1030P = 0.002P <0.0001Data from follow_time.sasSummary Statistics for Time: rando_lastfup_cens_monfirst interim analysisP = 0.5Slamon D., SABCS 2006
22Mean LVEF - All Observations 2nd Interim Analysis 6665TCH64AC->T63LVEF points %62AC->TH616059581002003004005006007008009001000AC->T (N=1014)AC->TH (N=1042)Time since randomization (days)TCH (N=1030)Slamon D., SABCS 2006
23NEOADJUVANT TREATMENT January 2007 – April 2007: Trastuzumab + Docetaxel + Carboplatin x 6 cyclesMay 2007 QUART SEminimal residual disease ; 15 N –Trastuzumab for a total of 1 year course+ aromatase inhibitor