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Goals of Neoadjuvant Theapy in Breast Cancer
• To improve surgical outcomes and options
- For operable breast cancer, the aim is to increase the chance of breast conserving surgery in patients who would otherwise require mastectomy
X+D+H
AT → T → CMF + H
D + V + T (including IBC) D+H D + cisplatin + H (including IBC) V + H (including IBC)
Trastuzumab NOAH, all patients
NOAH, IBC only Lapatinib
.
.
.
Conclusions from Run-in Phase (N=60)
• Neutropenia Grade III/ IV in 82%
G-CSF made mandatory together with L
• Treatment discontinuations in 34.5%
.
pCR (%)
FEC, 5-fluorouracil, epirubicin, cyclophosphamide
The MD Anderson Study
BC pts
Paclitaxel q3wk x 4 N=19
FEC x 4
M0, T1-3, No-1,
HER2+
R
(FISH or ICH 3+)
EFS: HER2-positive population
.
L. Gianni et al., The Lancet, 2010
… Future Clinical Practice….
.
Anti-HER2 Treatment: mechanisms of action
.
Three Neoadjuvant Trials Using Targeted Therapies for HER-2 Positive BC
H+T q3w x 4 cycles
T q3w x 4 cycles
H q3w x 4 cycles + CMF q4w x 3 cycles
CMF q4w x 3 cycles
Surgery followed by radiotherapya
H continued q3w to week 52
Surgery followed by radiotherapya
.
Buzdar AU, Clin Cancer Res 2007
Buzdar A et al ASCO Breast 2009
NOAH
HER2-positive LABC (IHC 3+ or FISH+)
(n=115)
H + AT q3w x 3 cycles
(n=113)
AT q3w x 3 cycles
pCR to Neoadjuvant Chemotherapy is correlated with improved DFS & OS
(NSABP B-27)
Disease free-survival
Overall Survival
ቤተ መጻሕፍቲ ባይዱ
.
Bear HD, et al. J ClinOncol. 2006;24(13):2019-2027.
Untch M, Loibl S, Bischoff J, Eidtmann H, Kaufmann M, Blohmer JU, Hilfrich J, Strumberg D, Fasching P, Kreienberg R, Tesch H, Hanusch C, Gerber B, Rezai M, Jackisch C, Huober J, Kühn T, Nekljudova V, von
.
NSABP B-18
1523 pts with clinical T1-3, N0-N1 breast cancer
Stratification • Age • Clinical Tumor Size • Clinical Nodal Status
Operation
AC x 4
AC x 4
Operation
pCR rates in the NOAH trial: intent-to-treat population
Patients 50 (%)
40
30
20
10
0
39%
p=0.002
20%
With H
Without H
HER2 positive
.
Gianni L et al. Lancet 2010; 375: 377–84
OPEN ISSUES IN MULTIDISCIPLINARY BREAST CANCER MANAGEMENT Mediterranean School of Oncology Rome, March 30, 2012
NEOADJUVANT THERAPY
Lucia Mentuccia Oncologia Medica, Sora
.
Wolmark N t al; J Natl Cancer Inst Monogr. 2001
NSABP B-18:
Clinical and Pathologic Breast Tumor Response
cCR (249 pts)
cPR (296 pts) cSD + cPD (140 pts)
40
32
Mast Lump
60
68
P < 0.01
Postop-Chemo Preop- Chemo
.
Wolmark N t al; J Natl Cancer Inst Monogr. 2001
.
Wolmark N t al; J Natl Cancer Inst Monogr. 2001
.
.
L dose reduced from 1250 to 1000 mg/ d
• Diarrhea Grade III/ IV in 6.9%
Loperamide given as stand-by medication for L
.
San Antonio Breast Cancer Symposium - Cancer Therapy and Research Center at UT Health Science Center – December 8-12, 2010
LAPATINIB VS TRASTUZUMAB IN COMBINATION WITH NEOADJUVANT ANTHRACYCLINE-TAXANE-BASED CHEMOTHERAPY: PRIMARY EFFICACY ENDPOINT ANALYSIS OF THE GEPARQUINTO STUDY (GBG 44)
Study Pernas et al 2006, n=16 Buzdar et al 2007, n=64 Coudert et al 2005, n=33 Lybaert et al 2006, n=89 Gianni et al 2007, n=115 Limentani et al 2007, n=31 Griggs et al 2005, n=18 Hurley et al 2002, n=48 Harris et al 2003, n=40
AC → T + H (including IBC)
T + H (including IBC)
D+H
AT → T → CMF + H (IBC only)
T + L (IBC only)
0 10 20 30 40 50 60 70 80 90 100
L, lapatinib; V, vinorelbine; X, capecitabine;
Minckwitz G for the GBG /AGO study group
.
This presentation is the intellectual property of the author/presenter Contact them for permission to reprint and/or distribute.
19 crossed over to H
HER2-negative LABC (IHC 0/1+)
(n=99)
AT q3w x 3 cycles
T q3w x 4 cycles
CMF q4w x 3 cycles
Surgery followed by radiotherapya
.
Gianni L et al. Lancet 2010; 375: 377–84
.
2411 pts
NSABP B-27
Pts with T1c-3 N0 or T1-3N1 breast cancer
Randomization
AC x 4 Tam X 5 Yrs
Surgery
AC x 4 Tam X 5 Yrs
Taxotere x 4
Surgery
AC x 4 Tam X 5 Yrs
36% 43%