乳腺癌的新辅助治疗ppt课件

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
NSABP B-27: Overall Survival Nodal Status
Pts without pCR
.
Pts with pCR
NSABP B-27: OS, DFS, RFS
.
Preoperative vs postoperative, Overall Survival
.
The Cochrane Library, Issue 3, 2008
.
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 vs residual disease, Overall Survival
.
.
Intrinsic sub-types have different prognosis and different response to primary CT
.
Response Rates with Neoadjuvant Trastuzumab
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
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
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
.
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)
- 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
pCR to Neoadjuvant Chemotherapy is correlated with improved DFS & OS
(NSABP B-27)
Disease free-survival
Overall Survival
.
Bear HD, et al. J ClinOncol. 2006;24(13):2019-2027.
.
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)
36% 43%
9% 4%
23%
pCR (63 pts)
pNon-Inv (26 pts)
pInv (160 pts)
20%
.
Wolmark N t al; J Natl Cancer Inst Monogr. 2001
100 80 60
% 40 20 0
NSABP B-18:
Surgery Performed
OPEN ISSUES IN MULTIDISCIPLINARY BREAST CANCER MANAGEMENT Mediterranean School of Oncology Rome, March 30, 2012
NEOADJUVANT THERAPY
Lucia Mentuccia Oncologia Medica, Sora
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.
Kelly et al 2006, n=37 Burstein et al 2003, n=40
Bines et al 2003, n=32 Baselga et al 2007, n=31 Christofanilli et al 2006, n=30
T → FEC + H
T → FEC + H
D+H
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
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;
.
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
L dose reduced from 1250 to 1000 mg/ d
• Diarrhea Grade III/ IV in 6.9%
Loperamide given as stand-by medication for L
.
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
Surgery
Taxotere x 4
.
Bear HD, et al. J ClinOncol. 2006;24(13):2019-2027.
NSABP B-27 Pathologic Complete Response in
Breast
.
Bear HD, et al. J ClinOncol. 2006;24(13):2019-2027.
pCR with CT Trastuzumab
75
% of patients
50
20 26%
66%
0
T-FEC
T-FEC + Tras
.
Buzdar AU, Clin Cancer Res 2007
MD Anderson Neoadjuvant Trial DFS at 72 months FU
N=42
ห้องสมุดไป่ตู้
Paclitaxel q3wk x 4 + H x 12 N=23
FEC x 4 + H x 12
FEC, 5-fluorouracil, epirubicin, cyclophosphamide H, trastuzumab
.
Additional 22 pts
Buzdar AU, Clin Cancer Res 2007
.
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
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
.
.
.
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+)
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
.
.