Preoperative Chemotherapy, NSABP Protocols B-18 and B-27: an ...
Preoperative Chemotherapy, NSABP Protocols B-18 and B-27: an ...
Preoperative Chemotherapy, NSABP Protocols B-18 and B-27: an ...
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<strong>Preoperative</strong> <strong>Chemotherapy</strong>,<br />
<strong>NSABP</strong> <strong>Protocols</strong><br />
B-<strong>18</strong> <strong><strong>an</strong>d</strong> B-<strong>27</strong>:<br />
<strong>an</strong> update<br />
Norm<strong>an</strong> Wolmark
Adjuv<strong>an</strong>t Therapy
B-<strong>18</strong><br />
Duration: 88-93<br />
ACCRUAL: 1,523<br />
B-<strong>27</strong><br />
Duration: 95-00<br />
ACCRUAL: 2,411<br />
B-40<br />
pCR endpoint<br />
Started 11-06
B-<strong>18</strong><br />
OPERABLE BREAST CANCER<br />
FNA or Core<br />
OPERATION<br />
AC x 4<br />
Age, T, cN<br />
AC x 4<br />
OPERATION<br />
Tam for women ≥50 yrs. only
<strong>NSABP</strong> B-<strong>18</strong><br />
OPENED: Oct. 1988<br />
CLOSED: Apr. 1993<br />
ACCRUAL: 1,523<br />
MTS: 9.5 years (2001)<br />
16 years (present)
B-<strong>18</strong> Clin.Tumor/Node Status<br />
cm<br />
< 2.0<br />
2.1 - 4.0<br />
> 4.1<br />
%<br />
28<br />
59<br />
13<br />
Node neg. 74
Tumor Response
100%<br />
80%<br />
60%<br />
40%<br />
20%<br />
0%<br />
Tumor Response (685pts.)<br />
79<br />
CR cCR pCR
100%<br />
80%<br />
60%<br />
40%<br />
20%<br />
0%<br />
Tumor Response (685pts.)<br />
79<br />
36<br />
CR cCR pCR
100%<br />
80%<br />
60%<br />
40%<br />
20%<br />
0%<br />
Tumor Response (685pts.)<br />
79<br />
36<br />
13<br />
CR cCR pCR<br />
*25% pCR w DCIS
100%<br />
80%<br />
60%<br />
40%<br />
20%<br />
0%<br />
42<br />
Nodal Response<br />
60<br />
Post Pre<br />
NEG<br />
P < 0.01
100%<br />
80%<br />
60%<br />
40%<br />
20%<br />
0%<br />
60<br />
Operation<br />
68<br />
Post Pre<br />
Lx<br />
P < 0.01
Outcome
00%<br />
80%<br />
60%<br />
40%<br />
20%<br />
0<br />
Year<br />
B-<strong>18</strong> <strong>18</strong> DFS <strong><strong>an</strong>d</strong> Survival<br />
P = 0.5 P = 0.8<br />
Postop<br />
Preop<br />
Pts. Events<br />
751<br />
742<br />
338<br />
323<br />
2 4 6 8<br />
Postop<br />
Preop<br />
Pts.<br />
751<br />
742<br />
Events<br />
2<strong>18</strong><br />
221<br />
2 4 6 8<br />
JNCI Monographs #30 96 2001
100<br />
90<br />
80<br />
70<br />
60<br />
50<br />
40<br />
30<br />
DFS<br />
N Ev HR P<br />
Post 751 434<br />
Pre 742 410 .93 0.<strong>27</strong><br />
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16
100<br />
90<br />
80<br />
70<br />
60<br />
50<br />
40<br />
30<br />
DFS<br />
N Ev HR P<br />
Post 496 292<br />
Pre 487 255 .81 0.05<br />
0 1 2 3 4 0 1 2 3 4 5 6 7 8 9 10
100<br />
90<br />
80<br />
70<br />
60<br />
50<br />
40<br />
30<br />
Survival<br />
N Ev HR P<br />
Post 751 311<br />
Pre 742 308 .99 0.90<br />
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16
Treatment by Age<br />
Interaction
100<br />
90<br />
80<br />
70<br />
60<br />
50<br />
40<br />
30<br />
100<br />
90<br />
80<br />
70<br />
60<br />
50<br />
40<br />
30<br />
pCR <strong><strong>an</strong>d</strong> Outcome
%<br />
100<br />
80<br />
60<br />
40<br />
20<br />
0<br />
YEAR<br />
DFS<br />
pCR (88 pts.)<br />
pINV (159 pts.)<br />
cPR (295 pts.)<br />
cNR (140 pts.)<br />
P=0.00005<br />
0 1 2 3 4 5 6 7 8<br />
100<br />
80<br />
60<br />
40<br />
20<br />
0<br />
%<br />
JNCI Monographs #30 96 2001
100<br />
90<br />
80<br />
70<br />
60<br />
50<br />
40<br />
30<br />
N Ev HR<br />
No pCR 599 344<br />
pCR 86 29 .47<br />
DFS <strong><strong>an</strong>d</strong> pCR<br />
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16<br />
75<br />
52<br />
P
100<br />
90<br />
80<br />
70<br />
60<br />
50<br />
40<br />
30<br />
N Ev HR<br />
No pCR 599 263<br />
pCR 86 14 .28<br />
Survival <strong><strong>an</strong>d</strong> pCR<br />
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16<br />
86<br />
66<br />
P
RESPONDERS<br />
AC<br />
chemotherapy<br />
NON<br />
RESPONDERS
AC<br />
OPERATION<br />
B-<strong>27</strong><br />
OPERABLE BREAST CANCER<br />
Age, T, cN<br />
AC→Txt*<br />
*100mg/m² x 4; Tam for all<br />
AC<br />
OPERATION OPERATION<br />
Txt
<strong>NSABP</strong> B-<strong>27</strong><br />
OPENED: Dec. 1995<br />
CLOSED: Dec. 2000<br />
ACCRUAL: 2,411<br />
MTS: 6.5 years (2006 JCO)<br />
8.5 years (present)
B-<strong>27</strong>/<strong>18</strong> Clin.Tumor/Node Status<br />
cm<br />
< 2.0<br />
2.1 - 4.0<br />
> 4.0<br />
B<strong>27</strong><br />
15<br />
41<br />
45<br />
B<strong>18</strong><br />
28<br />
59<br />
13<br />
Node neg. 70 74
Tumor Response
40%<br />
20%<br />
0%<br />
Path Complete Response<br />
12.9<br />
AC AC>T<br />
pCR<br />
JCO Nov ‘03
40%<br />
20%<br />
0%<br />
Path Complete Response<br />
12.9<br />
26.1<br />
AC AC>T<br />
pCR<br />
P < 0.001<br />
JCO Nov ‘03
100%<br />
80%<br />
60%<br />
40%<br />
20%<br />
0%<br />
51<br />
Nodal Response<br />
58<br />
AC AC>T<br />
NEG<br />
P < 0.01
40%<br />
20%<br />
0%<br />
pCR: AC→T<br />
26 26 28 29<br />
23<br />
28<br />
24<br />
cN- cN+ 0-2 2.-4 4+ 50
%<br />
50<br />
45<br />
40<br />
35<br />
30<br />
25<br />
20<br />
15<br />
10<br />
5<br />
0<br />
13.8<br />
pCR <strong><strong>an</strong>d</strong> ER Status<br />
ER v treatment p=0.69<br />
22.7<br />
5.8<br />
14.1<br />
31<br />
Neg Pos Unk<br />
p=0.002<br />
p
% Node +<br />
70<br />
60<br />
50<br />
40<br />
30<br />
20<br />
10<br />
0<br />
pCR<br />
Nodes <strong><strong>an</strong>d</strong> Tumor Response<br />
13<br />
p
Outcome
100<br />
90<br />
80<br />
70<br />
60<br />
50<br />
40<br />
DFS<br />
N Ev RR P<br />
AC 784 304<br />
AC→T 783 292 .92 0.29<br />
0 1 2 3 4 5 6 7 8
100<br />
90<br />
80<br />
70<br />
60<br />
50<br />
40<br />
RFS*<br />
N Ev RR P<br />
AC 784 254<br />
AC→T 783 220 .83 0.04<br />
76.3<br />
70.8<br />
0 1 2 3 4 5 6 7 8<br />
*X Second Primary; X CBC
15<br />
10<br />
5<br />
0<br />
Local or IBTR<br />
AC<br />
AC→T p=0.016<br />
0 1 2 3 4 5 6 7 8<br />
Recurrence<br />
25<br />
20<br />
15<br />
10<br />
5<br />
0<br />
Dist<strong>an</strong>t<br />
0 1 2 3 4 5 6 7 8
100<br />
90<br />
80<br />
70<br />
60<br />
50<br />
40<br />
Survival<br />
N Ev RR P<br />
AC 784 192<br />
AC→T 783 <strong>18</strong>2 .93 0.46<br />
ACSx→ T 777 <strong>18</strong>9 .97 0.76<br />
0 1 2 3 4 5 6 7 8
pCR <strong><strong>an</strong>d</strong> Outcome
100<br />
90<br />
80<br />
70<br />
60<br />
50<br />
40<br />
pCR v no pCR<br />
HR 0.45<br />
P
100<br />
90<br />
80<br />
70<br />
60<br />
50<br />
40<br />
pCR v no pCR<br />
HR 0.33<br />
P
% Disease-Free<br />
0 20 40 60 80 100<br />
#N %<br />
0 47<br />
1-3 32<br />
4-9 16<br />
10+ 5<br />
B-<strong>27</strong> DFS<br />
no pCR <strong><strong>an</strong>d</strong> Nodes (<strong>18</strong>81)<br />
0 2 4 6 8<br />
Years after R<strong><strong>an</strong>d</strong>omization<br />
0<br />
1-3<br />
4-9<br />
10+
Txt Resp<br />
Txt Non-R<br />
N=24<br />
Txt 100mg/m 2 q3w x 4<br />
92 genes correlated<br />
with Txt response<br />
(p=0·001)<br />
Jenny Ch<strong>an</strong>g<br />
L<strong>an</strong>cet 362 ’03
Tissue for<br />
Biomarkers<br />
R<br />
a<br />
n<br />
d<br />
o<br />
m<br />
i<br />
z<br />
e<br />
<strong>NSABP</strong> B-40<br />
Her2 Neg ≥2cm<br />
T x 4<br />
TX x 4<br />
TG x 4<br />
AC x 4<br />
AC x 4<br />
AC x 4<br />
± Bevacizumab x 6<br />
Tissue for<br />
Biomarkers<br />
Endpoints: pCR; 2 0 endpoint: pCR ∆ (29→38%)<br />
DFS N=1200 Started: 11-07<br />
S<br />
u<br />
r<br />
g<br />
e<br />
r<br />
y<br />
±<br />
B evacIzu<br />
m ab
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p<br />
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r<br />
a<br />
b<br />
l<br />
e<br />
B<br />
C<br />
R<br />
AC X 4<br />
AC X 4<br />
AC X 4<br />
<strong>NSABP</strong> B-41<br />
Her2 Pos<br />
N=522; pCR ∆ 22% (42→64%)<br />
Paclitaxel/wk +<br />
Trastuzumab<br />
Paclitaxel/wk +<br />
Lapatinib<br />
Paclitaxel/wk +<br />
Lapatinib +<br />
Trastuzumab<br />
S<br />
u<br />
r<br />
g<br />
e<br />
r<br />
y<br />
T<br />
m<br />
a<br />
b
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