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1、P. Neven GYN ONCOL & MBC, UZ-KULeuven,Ongoing Clinical Research & Trials Multidisciplinary Breast Centre,May 2007,Ten most frequently occuring tumours in Flanders, 2000 - 2001,Source: Vlaams Kankerregistratienetwerk, VLK,Age-specific incidence of breast cancer in women, Flanders, 1997-2001,Source: V
2、laams Kankerregistratienetwerk, VLK,SABCS 2006 2003: A decrease in breast cancer incidence,May be the incidence will come down?,I. Ongoing Clinical Trials,May 2007,II. Ongoing MBC Research Projects,Prevention, Adjuvant, Metastatic,I. Clinical Trials,May 2007,Completed, Recruiting, Future Trials,Endo
3、crine Therapy, Chemotherapy, Targeted Therapy,Recently Closed Clinical Trials,May 2007,Adjuvant: BIG-1-98, TEAM, (E-)ZOFASTTACT, FEC-TXT (dd), Caelyx-EndoxanHERA, AC-AT, Metastatic: Lapatinib trials, Tam + Iressa,EFECT, Lapatinib + Zarnestra, Radiotherapy: MSP-trial,Recruiting Clinical Trials,May 20
4、07,Prevention: IBIS-2 DCIS/High RiskNeo- Adjuvant: Taxotere-Xeloda-HerceptinAdjuvant: SOFT, TEXT, TAGAS,Pregnancy (pharmacokinetics & outcome)Metastatic: MoAb IGF-1R, FINDER-2, Vinflunin, Oral Navelbine,Xeloda +/- Sutent, BIBW, HKIEye trial (Maxidex vs Lacrystat Taxotere related dacrocystostenosis),
5、Future Clinical Trials,May 2007,Neo- Adjuvant: Neo-AlltoNeoadjuvant Paclitaxel + Herceptin +/- PertuzumabAdjuvant: Fertility trial, SOLE, ALTTOMINDACT, CASAMetastatic: Lapatanib +/- Pazopanib,Recruiting Clinical Trials,IBIS-2 DCIS (tamoxifen standard)High Risk (placebo standard),0,10,20,30,40,50,21,
6、T (n=3116),A (n=3125),48,Number of cases,12,T (n=2372),E (n=2352),26,T (n=2575),L (n=2582),26,14,ATAC IES MA17 BIG 1-98,T (n=4007),L(n=4003),28,16,Incidence of Contralateral Breast Cancers,Aromatase Inhibitors versus Tamoxifen,Why IBIS-II? Prevention,Breast Cancer Prevention Postmenopausal Women,Ong
7、oing Clinical Trials,May 2007,IBIS-2: 20 countries recruiting Prevention: Placebo vs Anastrozole 36/1516 ER+ DCIS: Tamoxifen vs Anastrozole 63/1014,Late age 1st pregnancy, parity, age menopause, breast density, familial history, LCIS, ADH Subprotocol: Bone, Lipid, Cognitive function,IBIS-2 Recruitin
8、g Centres,St.Luc Brussel St.Pierre Brussel VUB Brussel Virga Jesse Hasselt St.Elisabeth Namen St.Augustinus Wilrijk Erasmus Brussel Bordet Brussel Heilig Hart Leuven OLVrouwZH Aalst ZOL Genk Clinique St.Pierre Ottignies CHR Citadelle Luik Brugmann Brussel Centre Hospitalier de lArdenne,If you have s
9、mall cell LCIS, NSABP-P1 included 850 such patients 7-years of follow-up Tamoxifen versus Placebo Events13 (Tam) vs 38 (Placebo) If placebo: incidence of event is 1-2%,Recruiting Clinical Trials,FINDER-II2nd line Metastatic Endocrine,First Line: TTP Benefit of Fulvestrant over Tamoifen in ER+ & PgR+
10、 Patients*,Howell et al. JCO 2004; 22: 1605-13,Proportion not progressed,TTP (days),Hazard ratio = 0.85 CI (0.631.15); p=0.31,Median TTP: Fulvestrant: 11.4 months Tamoxifen: 8.5 months,*Retrospective analysis,ORR F 44.3% vs T 29.8%; p=0.02,Fulvestrant 250 mg/month Provides Long-term Downregulation o
11、f ER Levels,Gutteridge et al. SABCS 2004,Mean ER H-score,Time on treatment,Pre-treatment (n=29),300,250,200,150,100,50,0,4-6 weeks (n=26),6 months (n=20),PD (n=8),p=0.01,p=0.001,Fulvestrant induces dose-related ER downregulation (PgR and Ki67)*,Robertson et al. Cancer Res 2001; 61: 67396746,Placebo
12、(n=29),Fulvestrant 50 mg (n=31),Fulvestrant 125 mg (n=32),Fulvestrant 250 mg (n=32),13%,39%,50%,59%,Change from baseline (%),125,136,124,113,Pre-treatment mean H-score,*Data not shown,Finder-II,Fulvestrant HD,135 postmenopausal women with HR+ ABC after failure on one prior endocrine therapy,Progress
13、ion,3-monthly follow-up,Endpoints TTP (primary) ORR CB Safety,Fulvestrant LD,HD, high-dose (500 mg IM on Day 0, 500 mg on Days 14 and 28 and 500 mg every 28 3 days thereafter) LD, high-dose (500 mg IM on Day 0, 250 mg on Days 14 and 28 and every 28 3 days thereafter) AD, approved dose (250 mg IM eve
14、ry 28 3 days),Randomisation 1:1,Fulvestrant AD,Finder II Overview of Eligibility (2nd line Breast Cancer Treatment),12 Month gap,Yes,Yes,No,KEYAdjuvant TreatmentEligible (randomised into study)Not EligibleFirst Line TreatmentR = Recurrence P = Progression,Patients who previously received adjuvant tr
15、eatment,Yes,Patients who were diagnosed with Advanced Breast Cancer,Eligible?,R,R,R,R,P,Yes,P,EBC,ABC,Regulatory Definition of 2nd line Breast Cancer,Current & Future Clinical Trials Targeted Therapies,ALTTOAdjuvant,Two Targets, One Drug Lapatinib Profile,Lapatinib is a novel oral dual-tyrosine kina
16、se inhibitor with specificity for the ErbB-1 and ErbB-2 receptors Belongs to the 4-anilinoquinazoline class of tyrosine kinase inhibitors Binds reversibly to the cytoplasmic ATP-binding site of the kinase, thereby preventing receptor phosphorylation and activation,N-3-Chloro-4-(3-fluorobenzyl)oxyphenyl-6- 5-(2(methylsulfonyl)ethylaminomethyl)-2-furyl- 4-quinazolinamine,
