B-31/N9831 First Interim Joint Analysis

1
B-31/N9831 First Interim Joint Analysis

• NSABP Meeting
• Baltimore MD
• 17 September 2005
• Edward H. Romond, M.D.

2
NSABP B-31
Control AC?T
Arm 1
Arm 2
NCCTG N9831
Arm A
Investigational AC?TH
Arm B
Arm C
doxorubicin/cyclophosphamide (AC) 60/600 mg/m2
q 3 wk x 4
paclitaxel (T) 175 mg/m2 q 3 wk x 4
paclitaxel (T) 80 mg/m2/wk x 12
trastuzumab (H) 4mg/kg LD 2 mg/kg/wk x 51
3
Joint Analysis Flow Diagram
B-31 2043
N9831 2766

• Trial
• Number Registered1
• Treatment Arm
• Number Randomized
• Accepted / Refused Protocol Therapy
• (follow-up pending)4
• Number with follow-up4
• Total per arm with follow-up
• Joint Analysis Cohort

1006 (142) 864
18 (10) 8
1015 (152) 863
4 (3) 1
13 (9) 4
806 (3) 803
809 (1) 808
5 (5) 0
A 819
C 814
(A')2 (152)
(B)3 (981)
1 1024
2 1019
/
/
/
/
872
864
807
808
1679
1672
Group 1 AC?PTX
Group 2 AC?PTXH
Total in Intent-to-Treat Comparison
3351
1 B-31 as of 2/15/2005 N9831 as of 11/1/2004 2
(A') Randomized to Arm A 2/1/10029/3/2002
while Arm C was closed to accrual excluded from
joint analysis 3 (B) Excluded from joint
analysis 4 B-31 as of 2/15/2005 N9831 as of
3/15/2005
4
Patient and Tumor Characteristics ()
AC ? Paclitaxel AC ? Paclitaxel AC ? Paclitaxel Trastuzumab AC ? Paclitaxel Trastuzumab
872 B-31 807 N9831 864 B-31 808 N9831
Age lt50 50-59 60 52 34 15 51 34 15 51 32 16 50 32 18
No. Pos Nodes 0 1-3 4-9 10 0 57 29 14 13 48 25 15 0 57 29 14 11 50 25 14
Hormone Receptors ER ER- PR PR- 53 47 41 58 52 46 41 57 51 48 39 60 51 48 39 60
Tumor Size 2.0 cm. 2.1-4.0 cm. gt4.0 cm. 41 43 14 40 46 13 37 44 17 38 47 14
5
Disease-Free Survival
AC?TH
87
85
AC?T
75

67
N Events AC?T 1679 261 AC?TH 1672 134
HR0.48, 2P3x10-12
Years From Randomization
B31/N9831
6
Forest Plot For Disease-Free Survival
ALL DATA
Age
60 50-59 40-49 39
Positive Negative
Hormone Receptor
4.1cm 2.1- 4.0 cm lt2.0 cm
Tumor Size
No. Positive Nodes
10 4-9 1-3 0
Protocol
N9831 NSABP B-31
0.2
0.4
0.6
0.8
1.0
1.2
1.4
Hazard Ratio
7
N9831/B-31 Disease Free Survival By Age
8
N9831/B-31 DSF By HR Status
9
B-31/N9831 Disease Free Survival By Path Tumor
Size
A lt 2.0cm
B 2.1-4.0cm
90
90
70
70
50
50
0
1
2
3
4
5
0
1
2
3
4
5
C gt 4.1cm
90
70
50
0
1
2
3
4
5
10
B-31/N9831 Disease Free Survival By Nodal Status
11
Disease-Free Survival
B-31
N9831
AC?TH
AC?TH
87
87
AC?T
85
86
AC?T
78
74

66
68
N Events
N Events
AC?T 807 90
AC?T 872 171
AC?TH 808 51
AC?TH 864 83
HR0.55, 2P0.0005
HR0.45, 2P1x10-9
Years From Randomization
12
Time to First Distant Recurrence
100
AC?TH
AC-gtTH
90
90
90
90
90
90
90
AC?T
AC-gtT
80
81
81
81

74
74
74
70
N Events
N Events
AC?TH 1672 96 AC?T 1679 194
AC-gtT 1679 194
60
AC-gtTH 1672 96
HR0.47, 2P8x10-10
HR0.47, 2P8x10-10
50
0
1
2
3
4
5
B31/N9831
Years From Randomization
13
Hazard of Distant Recurrence
120
100
AC?T
80
Rate per 1000 Women /Yr
60
40
AC?TH
20
0
0
1
2
3
4
B31/N9831
Years From Randomization
14
B-31/N9831 Survival
AC?TH
94
91
AC?T
92
87
N Deaths AC?T 1679 92 AC?TH 1672 62
HR0.67, 2P0.015
Years From Randomization
B31/N9831
15
B-31 HER-2 Retesting atControl Reference Lab
(Lab Corp)Initial Test Done at Smaller Volume
Labs
Initial Submitted Result Central Herceptest not 3 Central Path Vysion FISH Neg. Both Central Assays Neg.
Herceptest 3 Other IHC pos. 10/52 11/23 12/52 9/23 10/52 (19) 8/23 (35)
Total 21/75 21/75 18/75 (24)

Less than 100 assays/month
Paik et al. J Natl Cancer Inst 94852-854, 2002
16
HER-2 Retesting atControl Reference Lab (Lab
Corp)Initial Test Done at Large Volume Labs
Initial Submitted Result Central Herceptest not 3 Central FISH (PathVysion) Neg Both Central Assays Neg.
Herceptest 3 Other IHC pos. 1/28 0/1 1/28 0/1 1/28 (4) 0/1 (0)
Total 1/29 1/29 1/29 (3)

More than 100 assays/month
Paik et al. J Natl Cancer Inst 94852-854, 2002
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B-31Central Review of Cases Entered by FISH
26/27 cases by PathVysion, 1/27 case by Inform
test
18
Central Review of Cases Entered After Amendment
(N240)
two cases with increase in both HER2 and CEP17
signals were regarded as amplified since both
PathVysion and Inform HER2 test were allowed for
eligibility
Paik, et al. Breast Cancer Res Treat 2002
76(suppl 1) S31 (abstr 9)
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B-31
N9831

• Edward Romond
• John Bryant
• Charles Geyer
• Elizabeth Tan-Chiu
• Soon Paik
• Sandra Swain
• Louis Fehrenbacher
• Victor Vogel
• Greg Yothers
• Ann Brown
• Terry Mamounas
• Norman Wolmark

• Edith Perez
• Vera Suman
• Nancy Davidson
• Silvana Martino
• Peter Kaufman
• Thomas Pisansky
• Leila Kutteh
• Daniel Visscher
• Robert Jenkins
• Shakir Dakhil
• Wilma Lingle
• James Ingle

Genentech Pamela Klein