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San Antonio Breast Cancer Symposium, December 8-12, 2015
Event-free and overall survival
following neoadjuvant weekly paclitaxel
and dose-dense AC +/- carboplatin
and/or bevacizumab in triple-negative
breast cancer: outcomes from
CALGB 40603 (Alliance)
William M Sikov, Donald A Berry, Charles M Perou, Baljit Singh,
Constance T Cirrincione, Sara M Tolaney, George Somlo,
Elisa R Port, Rubina Qamar, Keren Sturtz, Eleftherios Mamounas,
Mehra Golshan, Jennifer R Bellon, Deborah Collyar, Olwen M Hahn,
Lisa A Carey, Clifford A Hudis, Eric P Winer for the CALGB/Alliance
This presentation is the intellectual property of the authors. Contact them at [email protected] for permission to reprint and/or distribute.
San Antonio Breast Cancer Symposium, December 8-12, 2015
CALGB40603:
40603:Schema
Schema––Randomized
Randomized
Phase
CALGB
phase
II II
Arm
Paclitaxel 80 mg/m2 wkly x 12 ddAC x 4 A
Paclitaxel 80 mg/m2 wkly x 12 ddAC x 4 B Surgery&*
Bevacizumab 10 mg/kg q2wks x 9
XRT*
2X2
Randomization
mg/m2
Paclitaxel 80
wkly x 12
Carboplatin AUC 6 q3wks x 4
No Adjuvant
ddAC x 4
C Systemic
Treatment
Planned*
2 weekly
2 wkly xx12
Paclitaxel 80
80mg/m
Paclitaxel
mg/m
12 ddAC x 4
Research
biopsiesfrozen and
fixed
Carboplatin AUC 6 q3wks x 4
Bevacizumab 10 mg/kg q2wks x 9
D
&Research
biopsies if
residual tumor
*MD discretion
This presentation is the intellectual property of the authors. Contact them at [email protected] for permission to reprint and/or distribute.
San Antonio Breast Cancer Symposium – Cancer Therapy and Research Center at UT Health Science Center December 8-12, 2015
CALGB 40603 – pCR Results by factor
pCR Breast ypT0/is (%, 95% CI)
Overall
53 (49-58)
Carbo
60 (54-66)
Bev
59 (52-65)
No Carbo
46 (40-53)
No Bev
48 (41-54)
pCR Breast/Axilla ypT0/is ypN0 (%, 95% CI)
Overall
Carbo
No Carbo
54 (48-61)
41 (35-48)
48 (43-53)
Bev
52 (45-58)
No Bev
44 (38-51)
OR
1.76
OR
1.58
p-value
0.0018
p-value
0.0089
OR
1.71
p-value
0.0029
OR
1.29
p-value
0.0570
Sikov et al, J Clin Oncol 2015
This presentation is the intellectual property of William Sikov, MD. Contact at [email protected] for permission to reprint or distribute.
San Antonio Breast Cancer Symposium, December 8-12, 2015
CALGB 40603 – Long-term follow-up
Definition of endpoints
• Event-free survival (EFS) – Study entry to ipsilateral invasive
breast or other locoregional recurrence, distant recurrence or
death from any cause
• Overall Survival (OS) – Study entry to death from any cause
Median follow-up: 39 months (maximum 66 months)
110 EFS events and 77 OS deaths
• Data on systemic treatment received in adjuvant setting (if any)
was not collected
This presentation is the intellectual property of the authors. Contact them at [email protected] for permission to reprint and/or distribute.
San Antonio Breast Cancer Symposium, December 8-12, 2015
CALGB 40603 – Event-Free and Overall Survival
This presentation is the intellectual property of the authors. Contact them at [email protected] for permission to reprint and/or distribute.
San Antonio Breast Cancer Symposium, December 8-12, 2015
CALGB 40603 – EFS and OS by Response
Yes/No N (%)
pCR Breast
pCR
Breast/Axilla
pCR
Breast/Axilla
or RCB I*
231 (52%)
/212 (48%)
207 (47%)
/236 (53%)
266 (60%)
/177 (40%)
EFS-HR
0.33 (0.22-0.50) 0.30 (0.19-0.46) 0.29 (0.20-0.43)
OS-HR
0.28 (0.17-0.46) 0.20 (0.11-0.36) 0.21 (0.13-0.34)
* RCB I = Residual Cancer Burden Class I per Symmans et al, JCO 2007
This presentation is the intellectual property of the authors. Contact them at [email protected] for permission to reprint and/or distribute.
San Antonio Breast Cancer Symposium, December 8-12, 2015
CALGB 40603 – EFS by pCR Breast/Axilla
This presentation is the intellectual property of the authors. Contact them at [email protected] for permission to reprint and/or distribute.
San Antonio Breast Cancer Symposium, December 8-12, 2015
CALGB 40603 – OS by pCR Breast/Axilla
This presentation is the intellectual property of the authors. Contact them at [email protected] for permission to reprint and/or distribute.
San Antonio Breast Cancer Symposium, December 8-12, 2015
Impact of pCR Breast/Axilla on EFS in TNBC
FDA-requestedCALGB
meta-analysis
From meta-analysis;
40603 superimposed
pCR rates 47.8% (40603)
vs. 33.6% (meta-analysis)
Cortazar et al Lancet 2014
This presentation is the intellectual property of the authors. Contact them at [email protected] for permission to reprint and/or distribute.
San Antonio Breast Cancer Symposium, December 8-12, 2015
CALGB 40603 – EFS/OS Events by Response
• At 3 years, patients who achieved pCR Breast/Axilla
(47% overall) had much lower rates of
– Ipsilateral invasive breast recurrences
2.9% (vs 13.3%)
– Other locoregional recurrences
1.5% (vs. 6.6%)
– Distant recurrences
9.2% (vs. 26.5%)
– All deaths
6.8% (vs. 28.3%)
– Breast cancer attributed deaths
5.8% (vs. 25.2%)
This presentation is the intellectual property of the authors. Contact them at [email protected] for permission to reprint and/or distribute.
San Antonio Breast Cancer Symposium, December 8-12, 2015
CALGB 40603 – EFS and OS by Factor
Carboplatin
3-year
Bevacizumab
Yes
No
Yes
No
76%
71%
75%
72%
EFS
HR
3-year
0.84 (0.58-1.22)
0.80 (0.55-1.17)
81%
85%
85%
81%
OS
HR
1.15 (0.74-1.79)
0.76 (0.49-1.19)
This presentation is the intellectual property of the authors. Contact them at [email protected] for permission to reprint and/or distribute.
San Antonio Breast Cancer Symposium, December 8-12, 2015
CALGB 40603 – EFS for carboplatin vs. not
This presentation is the intellectual property of the authors. Contact them at [email protected] for permission to reprint and/or distribute.
San Antonio Breast Cancer Symposium, December 8-12, 2015
CALGB 40603 – EFS for bevacizumab vs. not
This presentation is the intellectual property of the authors. Contact them at [email protected] for permission to reprint and/or distribute.
San Antonio Breast Cancer Symposium, December 8-12, 2015
∆pCR Breast/Axilla vs. predicted EFS HR in TNBC
Derived from Cortazar et al
Adapted from Berry & Hudis,
JAMA Oncology 2015
This presentation is the intellectual property of the authors. Contact them at [email protected] for permission to reprint and/or distribute.
San Antonio Breast Cancer Symposium, December 8-12, 2015
CALGB 40603 – EFS/OS Events by Factor
Event type
Overall
Factor
Carbo
No Carbo
Bev
No Bev
Patients
443
225
218
222
221
EFS Events
109
52
57
50
59
Ipsilateral Inv Br Rec
36
14
22
13
23
Other LRR
18
7
11
8
10
Distant Recurrence
80
40
40
40
40
79
43
36
35
44
Breast Cancer Death
70
38
32
32
38
Non-BC, non-Rx Death
4
3
1
1
3
Unknown Death
5
2
3
2
3
OS Events
This presentation is the intellectual property of the authors. Contact them at [email protected] for permission to reprint and/or distribute.
San Antonio Breast Cancer Symposium, December 8-12, 2015
CALGB/Alliance 40603:
CALGB/Alliance
40603: Summary
Conclusions
• Achievement of pCR with weekly paclitaxel followed by ddAC
+/- carboplatin and/or bevacizumab is associated with significant
improvements in EFS and OS
• Addition of RCB I patients does not diminish the prognostic
significance associated with pCR Breast/Axilla
– Substantial reductions are seen in both LRR and DR
– Inferior outcomes are seen in clinical stage III disease with
failure to achieve a pCR and in clinically node-positive patients
with persistently positive axillary LNs after NACT
Results are consistent with the FDA-requested meta-analysis
This presentation is the intellectual property of the authors. Contact them at [email protected] for permission to reprint and/or distribute.
San Antonio Breast Cancer Symposium, December 8-12, 2015
CALGB/Alliance 40603:
CALGB/Alliance
40603: Summary
Conclusions
• Our study was underpowered to determine whether the
increases in the pCR rates seen with the addition of carboplatin
and bevacizumab improve EFS or OS
• Previous studies (BEATRICE, E5103, GeparQuinto, NSABP B-40)
have failed to demonstrate improvements in long-term outcomes
(EFS, RFS or OS with the addition of bevacizumab to a control
(neo)adjuvant chemotherapy regimen in stage I-III TNBC
• Results from other completed (GeparSixto) and ongoing
(BrighTNess, NRG-003) studies in the neoadjuvant and adjuvant
settings should help to clarify whether the addition of carboplatin
benefits patients with early stage TNBC
This presentation is the intellectual property of the authors. Contact them at [email protected] for permission to reprint and/or distribute.