POST ASCO2007 EMLO ADJUVNS

1
POST ASCO-2007EMLO ADJUVÁNS

• Patyánik Mihály

2
KEMOTERÁPIA
3
A meta-analysis of taxanes in adjuvant
chemotherapy (ACT) of early breast cancer
(EBC)A. K. Nowak, T. Ferguson, N. R. Wilcken,
D. Ghersi. University of Western Australia,
Perth,WA,Australia

• VizsgálatokCALB-934,US Oncology, BCIRG-001, E-
  2197 ECTO, GEICAM-9906, HECOG,
  NSABP B- 28,
  FinHer, PACS-01, Taxit-216, BIG
  2-98
• Eredmény
• DSF T ? HR0.81(p?0.00001)
• OS T ? HR0.81(p ?0.00001)
• Toxicitás
• T ? (febrilis neutropenia,fatigue)
• Nincs adat
• D vagy P
• Regimen (hossz ?)
• T és Antr.(seq. vagy conc.)

4
Estrogen receptor expression and efficacy of
docetaxel in early breast cancer A pooled
analysis of 3,490 patients included in two
randomized trials.F. Andre, K. broglio, h.
roche, m. martin, F. Penault-Lorca, G. N.
Hortobagyi, D. A. Berry, L. Pusztai. MD Anderson
Cancer Center, houston, TX, United States
Ratio for docetaxel x ER interaction 1.04
(0.70-1.54) p0.86
Docetaxel is associated with a 31 and 30 risk
reduction of death in ER- and ER disease,
respectively
No evidence that the risk reduction for death
provided by Docetaxel is dependent on the level
of ER expression
5
Phase III study of doxorubicin-cyclophosphamide
followed by paclitaxel or docetaxel given every 3
weeks or weekly in operable breast cancer
Results of Intergroup Trial E1199.J. A. Sparano,
M. Wang, S. Martino, V. Jones, E. Perez, T.
Saphner, A. C. Wolff, G. W. Sledge, W. C. Wood,
NE. Davidson. Eastern Cooperative Oncology Group,
Bronx, NY, United States
Node-positive or high-risk node-negative,
operable stage II or IIIA
N4988
4 x paclitaxel (175 mg/m2) q3w
4 x AC q3w
12 x paclitaxel (80 mg/m2) q1w
4 x AC q3w
R
4 x docetaxel (100 mg/m2) q3w
4 x AC q3w
12 x docetaxel (35 mg/m2) q1w
4 x AC q3w
Statistically designed as a two-by-two (not a
one-by-four) trial Hormonal therapy given to ER
patients
Objective - evaluate different sequential taxane
regimens Paclitaxel vs docetaxel Q3W
vs QW schedule Primary/secondary
endpoints DFS/OS Secondary exploratory
comparisons Standard P3 arm versus other
experimental arms
Median follow-up 60.2 mo
6
Phase III study of doxorubicin-cyclophosphamide
followed by paclitaxel or docetaxel given every 3
weeks or weekly in operable breast cancer
Results of Intergroup Trial E1199.J. A. Sparano,
M. Wang, S. Martino, V. Jones, E. Perez, T.
Saphner, A. C. Wolff, G. W. Sledge, W. C. Wood,
NE. Davidson. Eastern Cooperative Oncology Group,
Bronx, NY, United States
4 x paclitaxel (175 mg/m2) q3w
4 x AC q3w
12 x paclitaxel (80 mg/m2) q1w
4 x AC q3w
R
4 x docetaxel (100 mg/m2) q3w
4 x AC q3w
N4988
12 x docetaxel (35 mg/m2) q1w
4 x AC q3w
Statistically designed as a two-by-two (not a
one-by-four) trial Hormonal therapy given to ER
patients
Objective - evaluate different sequential taxane
regimens Paclitaxel vs docetaxel Q3W
vs QW schedule Primary/secondary
endpoints DFS/OS Secondary exploratory
comparisons Standard P3 arm versus other
experimental arms
Median follow-up 60.2 mo
7
Phase III study of doxorubicin-cyclophosphamide
followed by paclitaxel or docetaxel given every 3
weeks or weekly in operable breast cancer
Results of Intergroup Trial E1199.J. A. Sparano,
M. Wang, S. Martino, V. Jones, E. Perez, T.
Saphner, A. C. Wolff, G. W. Sledge, W. C. Wood,
NE. Davidson. Eastern Cooperative Oncology Group,
Bronx, NY, United States
Primary comparisons No change since SABCS
2005 Taxanes are equally effective Taxane weekly
and 3-weekly schedules are equally effective
8
Phase III study of doxorubicin-cyclophosphamide
followed by paclitaxel or docetaxel given every 3
weeks or weekly in operable breast cancer
Results of Intergroup Trial E1199.J. A. Sparano,
M. Wang, S. Martino, V. Jones, E. Perez, T.
Saphner, A. C. Wolff, G. W. Sledge, W. C. Wood,
NE. Davidson. Eastern Cooperative Oncology Group,
Bronx, NY, United States
Secondary (4-way comparisons)
Secondary comparisons For DFS, P1 and D3 are
significantly superior to P3 Further details at
debrief meeting
HR gt 1 favors experimental arms
9
Phase III study of doxorubicin-cyclophosphamide
followed by paclitaxel or docetaxel given every 3
weeks or weekly in operable breast cancer
Results of Intergroup Trial E1199.J. A. Sparano,
M. Wang, S. Martino, V. Jones, E. Perez, T.
Saphner, A. C. Wolff, G. W. Sledge, W. C. Wood,
NE. Davidson. Eastern Cooperative Oncology Group,
Bronx, NY, United States
Incidence of worst-grade toxicity
All arms performed as expected with more
haematologic toxicities with the 3-weekly
Taxotere. Primary prophylaxis with G-CSF was not
allowed and secondary prophylaxis G-CSF was
allowed only for FN.
10
TRASTUZUMAB
11
Updated results of the combined analysis of NCCTG
N9831 and NSABP B-31 adjuvant chemotherapy
with/without trastuzumab in patients with
HER2-positive breast cancer.E. A. Perez, E. H.
Romond, V. J. Suman, J. Jeong, N. E. Davidson, C.
E. Geyer, S. Martino, E. P. Mamounas, P. A.
Kauffman, N. Wolmark, NCCTG/NSABP. Mayo Clinic,
Jacksonville, FL, United States
12
Updated results of the combined analysis of NCCTG
N9831 and NSABP B-31 adjuvant chemotherapy
with/without trastuzumab in patients with
HER2-positive breast cancer.E. A. Perez, E. H.
Romond, V. J. Suman, J. Jeong, N. E. Davidson, C.
E. Geyer, S. Martino, E. P. Mamounas, P. A.
Kauffman, N. Wolmark, NCCTG/NSABP. Mayo Clinic,
Jacksonville, FL, United States
13
Updated results of the combined analysis of NCCTG
N9831 and NSABP B-31 adjuvant chemotherapy
with/without trastuzumab in patients with
HER2-positive breast cancer.E. A. Perez, E. H.
Romond, V. J. Suman, J. Jeong, N. E. Davidson, C.
E. Geyer, S. Martino, E. P. Mamounas, P. A.
Kauffman, N. Wolmark, NCCTG/NSABP. Mayo Clinic,
Jacksonville, FL, United States
14
Updated results of the combined analysis of NCCTG
N9831 and NSABP B-31 adjuvant chemotherapy
with/without trastuzumab in patients with
HER2-positive breast cancer.E. A. Perez, E. H.
Romond, V. J. Suman, J. Jeong, N. E. Davidson, C.
E. Geyer, S. Martino, E. P. Mamounas, P. A.
Kauffman, N. Wolmark, NCCTG/NSABP. Mayo Clinic,
Jacksonville, FL, United States
15
Updated results of the combined analysis of NCCTG
N9831 and NSABP B-31 adjuvant chemotherapy
with/without trastuzumab in patients with
HER2-positive breast cancer.E. A. Perez, E. H.
Romond, V. J. Suman, J. Jeong, N. E. Davidson, C.
E. Geyer, S. Martino, E. P. Mamounas, P. A.
Kauffman, N. Wolmark, NCCTG/NSABP. Mayo Clinic,
Jacksonville, FL, United States
16
Updated results of the combined analysis of NCCTG
N9831 and NSABP B-31 adjuvant chemotherapy
with/without trastuzumab in patients with
HER2-positive breast cancer.E. A. Perez, E. H.
Romond, V. J. Suman, J. Jeong, N. E. Davidson, C.
E. Geyer, S. Martino, E. P. Mamounas, P. A.
Kauffman, N. Wolmark, NCCTG/NSABP. Mayo Clinic,
Jacksonville, FL, United States
17
Updated results of the combined analysis of NCCTG
N9831 and NSABP B-31 adjuvant chemotherapy
with/without trastuzumab in patients with
HER2-positive breast cancer.E. A. Perez, E. H.
Romond, V. J. Suman, J. Jeong, N. E. Davidson, C.
E. Geyer, S. Martino, E. P. Mamounas, P. A.
Kauffman, N. Wolmark, NCCTG/NSABP. Mayo Clinic,
Jacksonville, FL, United States
18
Neoadjuvant trastuzumab in locally advanced
breast cancer (NOAH) Antitumour and safety
analysis.L. Gianni, V. Semiglazov, G. M.
Manikhas, W. Eiermann, A. Lluch, S. Tjulandin, A.
Feyereislova, B. Vanhauwere, P. Valagussa, J.
Baselga. Fondazione IRCCS Istituto

• Módszer
• Her-2-poz4?AT(PAC)3?CMF/-TRAS(1 év)
• Her-2-neg4?AT(PAC)3?CMF
• Eredmény
• Her-2-poz/-TRAS
• ORR 81 vs 73 (p0.18)
• pCR 43vs 23 (p0.002)
• Her-2-neg
• ORR 66
• pCR 17

19
HER2 expression and efficacy of preoperative
paclitaxel and 5-fluorouracil, cyclophosphamide,
doxorubicin chemotherapy in breast cancer.L.
Pusztai, F. Andre, C. Mazouni, C. Liedtke, S.
Kau, D. Frye, M. Green, A. M. Gonzalez-Angulo, W.
F. Symmans, G. N. Hortobagyi. M.D. Anderson
Cancer Center, Houston, TX, United States

• Retrospektiv vizsgálat-543 beteg(20 HER2)
• Eredmény
• pCR HER233 vs. HER2-15
• 5 éves RFS(HER2) pCR94 vs. pCR-70
• pCR prediktorokER- status,High grade,
  heti Paclitaxel
  regimen,HER2
• pCR ( ER-) HER250 vs. HER2-30
• pCR ( ER) HER219 vs. HER2-6

20
The impact of hormone receptor status on
pathologic response of HER2-positive breast
cancer treated with neoadjuvant chemotherapy with
or without trastuzumab.F. Peintinger, A.
Buzdar, H. Kuerer, A. Gonzalez-Angulo, C. Hatzis,
L. Pusztai, F. Esteva, M. Green, G. Hortobagyi,
W. Symmans. The University of Texas M.D. Anderson
Cancer Cent, Graz, Austria

• Eredmény(Weekly T(PAC) /FEC plus trastuzumab
  folyamatban)

21
HORMONTERÁPIA
22
Could treatment with tamoxifen be superior to
aromatase inhibitors in early-stage breast cancer
after pharmacogenomic testing? A modeling
analysis.R. S. Punglia, E. P. Winer, J. C.
Weeks, H. J. Burstein. Dana-Farber Cancer
Institute, Boston, MA, United States

• Módszer
• Endoxifen szint mérése a cytochrome P450 CYP2D6
  enzim aktivitás tükrében(mutációk)
• Markov model-BIG 1-98
• Eredmény
• Mutáció hiányábanTamoxifen jobb lehet
• Mutáció hiányábangyakoribb a hohullám

23
Survival with adjuvant surgical oophorectomy and
tamoxifen in premenopausal women with operable
breast cancer.R. R. Love, N. V. Dinh, T. T. Quy,
N. D. Linh, E. M. Hade, G. S. Young, D. Jarjoura.
Ohio State University, Columbus, OH, United
States

• MódszerOophorectomia /- 5 év TAM
• Eredmény
• Teljes beteganyag
• DFS(10 év)62 vs 51
• OS(10 év)70vs.52
• ER pos
• DFS(5 és10 év) 83 vs. 61 és 66 vs. 47
• OS(5 és10 év) 88 vs,74 és 82 vs 74

24
International comparison of the
cost-effectiveness of 5 years letrozole or
anastrozole compared to 5 years tamoxifen for
early breast cancer in hormone receptor-positive
postmenopausal women Belgium, Canada, UK, and US
analyses.S. Kaura, J. Karnon, F. di Trapani.
Novartis, East Hanover, NJ, United States

• Módszer
• Markov model (BIG 1-98,ATAC)
• Felhhasznált paraméterek,gyógyszer ára,
  DSF,CL,CL remisszió,LR,LR remisszió, DM,terminal
  care
• Eredmény
• Letrozole vagy Anastrozole alkalmazása
  cost-effectiv
• A Letrozole és Anastrozole összehasonlítás csak
  indirekt módon-FACE tial

25
Optimal use of aromatase inhibitors for adjuvant
treatment of hormone-sensitive early breast
cancer Up front or sequenced after tamoxifen?J.
Cuzick, P. Sasieni, A. Howell. Cancer Research
UK, London, United Kingdom

• Eredmény

26
Aromatase Inhibitors (AI) for Elderly Patients
Efficacy, Compliance and Safety According to
Patient Age in the BIG 1-98 TrialDiana
Crivellari, Zhuoxin Sun, Alan S. Coates, Karen N.
Price, Beat Thürlimann, Henning Mouridsen, Louis
Mauriac, John F. Forbes, Monica
Castiglione-Gertsch, Aron Goldhirsch for the BIG
1-98 Collaborative and International Breast
Cancer Study Groups
27
Aromatase Inhibitors (AI) for Elderly Patients
Efficacy, Compliance and Safety According to
Patient Age in the BIG 1-98 TrialDiana
Crivellari, Zhuoxin Sun, Alan S. Coates, Karen N.
Price, Beat Thürlimann, Henning Mouridsen, Louis
Mauriac, John F. Forbes, Monica
Castiglione-Gertsch, Aron Goldhirsch for the BIG
1-98 Collaborative and International Breast
Cancer Study Groups
AEs-CSONT
28
Aromatase Inhibitors (AI) for Elderly Patients
Efficacy, Compliance and Safety According to
Patient Age in the BIG 1-98 TrialDiana
Crivellari, Zhuoxin Sun, Alan S. Coates, Karen N.
Price, Beat Thürlimann, Henning Mouridsen, Louis
Mauriac, John F. Forbes, Monica
Castiglione-Gertsch, Aron Goldhirsch for the BIG
1-98 Collaborative and International Breast
Cancer Study Groups
Aes-Nem Csont
29
Aromatase Inhibitors (AI) for Elderly Patients
Efficacy, Compliance and Safety According to
Patient Age in the BIG 1-98 TriaDiana
Crivellari, Zhuoxin Sun, Alan S. Coates, Karen N.
Price, Beat Thürlimann, Henning Mouridsen, Louis
Mauriac, John F. Forbes, Monica
Castiglione-Gertsch, Aron Goldhirsch for the BIG
1-98 Collaborative and International Breast
Cancer Study Groups
30
Aromatase Inhibitors (AI) for Elderly Patients
Efficacy, Compliance and Safety According to
Patient Age in the BIG 1-98 TriaDiana
Crivellari, Zhuoxin Sun, Alan S. Coates, Karen N.
Price, Beat Thürlimann, Henning Mouridsen, Louis
Mauriac, John F. Forbes, Monica
Castiglione-Gertsch, Aron Goldhirsch for the BIG
1-98 Collaborative and International Breast
Cancer Study Groups
31
Cardiovascular adverse events (AEs) during
adjuvant endocrine therapy for early breast
cancer using letrozole or tamoxifen updated
safety analysis of trial BIG 1-98 Alan S.
Coates, Henning Mouridsen, Zhuoxin Sun, Manuela
Rabaglio, Monica Castiglione-Gertsch, Beat
Thürlimann, Louis Mauriac, Karen N. Price, Marco
Colleoni, Ian Smith for the BIG 1-98
Collaborative and International Breast Cancer
Study Groups
32
Cardiovascular adverse events (AEs) during
adjuvant endocrine therapy for early breast
cancer using letrozole or tamoxifen updated
safety analysis of trial BIG 1-98 Alan S.
Coates, Henning Mouridsen, Zhuoxin Sun, Manuela
Rabaglio, Monica Castiglione-Gertsch, Beat
Thürlimann, Louis Mauriac, Karen N. Price, Marco
Colleoni, Ian Smith for the BIG 1-98
Collaborative and International Breast Cancer
Study Groups
33
Central assessment of ER, PgR and HER2 in BIG
1-98 evaluating letrozole vs. tamoxifen as
initial adjuvant endocrine therapy for
postmenopausal women with hormone
receptor-positive breast cancerBB Rasmussen, MM
Regan, AE Lykkesfeldt, P Dell'Orto, B Del Curto,
KL Henriksen, MG Mastropasqua, B Thürlimann, G
Vialefor the BIG 1-98 Collaborative Group and
the International Breast Cancer Study Group
(IBCSG)
34
Central assessment of ER, PgR and HER2 in BIG
1-98 evaluating letrozole vs. tamoxifen as
initial adjuvant endocrine therapy for
postmenopausal women with hormone
receptor-positive breast cancerBB Rasmussen, MM
Regan, AE Lykkesfeldt, P Dell'Orto, B Del Curto,
KL Henriksen, MG Mastropasqua, B Thürlimann, G
Vialefor the BIG 1-98 Collaborative Group and
the International Breast Cancer Study Group
(IBCSG)
35
Central assessment of ER, PgR and HER2 in BIG
1-98 evaluating letrozole vs. tamoxifen as
initial adjuvant endocrine therapy for
postmenopausal women with hormone
receptor-positive breast cancerBB Rasmussen, MM
Regan, AE Lykkesfeldt, P Dell'Orto, B Del Curto,
KL Henriksen, MG Mastropasqua, B Thürlimann, G
Vialefor the BIG 1-98 Collaborative Group and
the International Breast Cancer Study Group
(IBCSG)
36
Central assessment of ER, PgR and HER2 in BIG
1-98 evaluating letrozole vs. tamoxifen as
initial adjuvant endocrine therapy for
postmenopausal women with hormone
receptor-positive breast cancerBB Rasmussen, MM
Regan, AE Lykkesfeldt, P Dell'Orto, B Del Curto,
KL Henriksen, MG Mastropasqua, B Thürlimann, G
Vialefor the BIG 1-98 Collaborative Group and
the International Breast Cancer Study Group
(IBCSG)
37
Central assessment of ER, PgR and HER2 in BIG
1-98 evaluating letrozole vs. tamoxifen as
initial adjuvant endocrine therapy for
postmenopausal women with hormone
receptor-positive breast cancerBB Rasmussen, MM
Regan, AE Lykkesfeldt, P Dell'Orto, B Del Curto,
KL Henriksen, MG Mastropasqua, B Thürlimann, G
Vialefor the BIG 1-98 Collaborative Group and
the International Breast Cancer Study Group
(IBCSG)
38
Central assessment of ER, PgR and HER2 in BIG
1-98 evaluating letrozole vs. tamoxifen as
initial adjuvant endocrine therapy for
postmenopausal women with hormone
receptor-positive breast cancerBB Rasmussen, MM
Regan, AE Lykkesfeldt, P Dell'Orto, B Del Curto,
KL Henriksen, MG Mastropasqua, B Thürlimann, G
Vialefor the BIG 1-98 Collaborative Group and
the International Breast Cancer Study Group
(IBCSG)
39
SUGÁRTERÁPIA
40
Influence of sequencing of chemotherapy and
radiotherapy regarding adverse effects of the
cytostatic treatment Results of the ADEBAR
trial.H. L. Sommer, J. K. Jueckstock, E. Genss,
K. Annecke, B. Rack, D. Steinfeld-Birg, N.
Harbeck, M. Kiechle-Bahat, W. J. Janni, K.
Friese. I. Universitäts-Frauenklinik, München,
Germany

• Módszer
• 4 x EC 4 x T(D)
• Rt
• I-közben
• II.végén
• Eredmény
• Hospitalizáció I-32.7vs.II-27.9
• Kezelési ido nottI-37.7 v. II 31.6
• Dózis redukció I-15.7 vs. II.-20.2
• Nem szignifikáns?high risk betegnél elobb CT

41
Toxicity of concurrent radiotherapy with CMF
chemotherapy in the E-CMF adjuvant breast
carcinoma regimenD. N. Church, M. Flubacher, A.
Cameron, A. Bahl, J. Braybrooke. Bristol
Haematology and Oncology Centre, Bristol, United
Kingdom

• Módszer
• 4xEpi-ADM4CMF?-6CMF (NET trial)
• 4xEpi-ADM4CMF-RT
• Eredmény
• G3/4 neutropenia 54.5 vs. 15
• Febrile neutropenia 22 vs.14
• G3/4 cutan acut RT toxicitás 31.2 vs 0-4.5
  (irod.)
• Hospitalizáció 22.1 - átlag 8 nap (3-23)

42
ÉRDEKES TÉMÁK
43
Comparative analysis of bone marrow (BM)
micrometastasis (M) with sentinel lymph node
(SLN) status in early breast cancer (BRCa).M. P.
Patel, S. Saha, S. Ali, D. Iddings, D. Wiese, H.
Sankaran, M. Arora, T. Singh, T. Branigin, K.
Barber. Mclaren Regional Medical Center, Flint,
MI, United States

• Retrospectiv vizsgálat-251 beteg
• Eredmény(BM)
• SLN/- N.S.
• T1/T2 N.S.
• ER/PR N.S.
• HER2 N.S.

44
Detection of minimal residual disease (MRD) in
peripheral blood of primary breast cancer
patients Translational research in the SUCCESS
study.J. K. Jueckstock, B. Rack, E.
Thurner-Hermanns, H. Forstbauer, K. Pantel, H.
Ulmer, M. Beckmann, W. Lichtenegger, W. J. Janni,
K. Friese. Klinikum Innenstadt, Munich
University, Munich, Germany

• Módszer
• Csontveloi tumor sejt poz.?prognózis?
• Célperifériás vér vizsgálata
• Mintavétel az adj. CH elot(I) és után(II)
• Eredmény
• MRD I.-31 , II.-9
• 87 MRD (I)?II. MRD
• I.-MRD- ? II. 16 MRD
• Nincs kapcsolatT, N, HR statusz, G, Her2 statusz

45
The impact of epoetin-alpha on anemia, red blood
cell (RBC) transfusions, and survival in breast
cancer patients (pts) treated with dose-dense
sequential chemotherapy Mature results of an AGO
phase III study (ETC trial).V. Moebus, H. Lueck,
C. Thomssen, N. Harbeck, U. Nitz, R. Kreienberg,
C. Jackisch, A. Schneeweiss, J. Huober, A. du
Bois, M. Untch. Städt.Kliniken Frankfurt/M.-Höchst
, Frankfurt, Germany

• Eredmény
• Anemia.ETC vagy ETCEPO plt0.001
• Transfúsio
• EC-T(Pac.) 1
• ETC 28
• ETCEPO 13 (p lt0.001)
• EPO adása DFS-t és az OS-t nem befolyásolta

46
ONCOTYPE DX

• 21 gén( ER, LN-)
• 16 cancer gén
• 5 referencia gén
• Recurence score
• ? 18 Low-risk
• 18-30 Intermedier-risk
• ?31 High-risk
• TAILORx-Phase III trial