1 Advances in Neoadjuvant and Adjuvant Therapy Kathy S. Albain, MD, FACP Director, Breast Clinical Research Program Co-Director, Breast Oncology Center Director of the Thoracic Oncology Program Professor of Medicine, Stritch School of Medicine Loyola University Chicago Dr. Albain has financial relationships with commercial interests that produce healthcare-related products or services relevant to the content I am planning, developing presenting with Agendia, Novartis, PUMA, Genentech/Roche, Genomic Health and Nanostring.
33
Embed
Advances in Neoadjuvant and Adjuvant Therapy Kathy … · · 2014-02-11Advances in Neoadjuvant and Adjuvant Therapy Kathy S. Albain, MD, FACP ... healthcare-related products or
This document is posted to help you gain knowledge. Please leave a comment to let me know what you think about it! Share it to your friends and learn new things together.
Transcript
1
Advances in Neoadjuvant and Adjuvant Therapy
Kathy S. Albain, MD, FACP Director, Breast Clinical Research Program
Co-Director, Breast Oncology Center Director of the Thoracic Oncology Program
Professor of Medicine, Stritch School of Medicine Loyola University Chicago
Dr. Albain has financial relationships with commercial interests that produce
healthcare-related products or services relevant to the content I am planning, developing presenting with Agendia, Novartis, PUMA, Genentech/Roche, Genomic
Health and Nanostring.
2
Advances in Adjuvant and Neoadjuvant Therapy from the
2013 San Antonio Breast Cancer Symposium
Kathy S. Albain, MD, FACP
Professor of Medicine
Dean’s Senior Scholar
Loyola University Chicago Stritch School of Medicine
Anthra then T vs shorter anthra 0.86 (0.04) 0.0005
Anthra + taxane vs expanded
anthracycline alone
0.94 (0.06) 0.33
Lancet Dec 6, 2011
*Unselected for HER2 status
Albain KS. 11th Annual Best of San Antonio – Bench to Bedside 2014
ARM A
EC x 4 cycles -> T x 4 cycles q3 wks
ARM C
EC x 4 cycles -> T x 4 cycles q2
+ Pegfilgrastim
ARM B
FEC x 4 cycles -> T x 4 cycles q3 wks
ARM D
FEC x 4 cycles -> T x cycles 4 q2
+ Pegfilgrastim
GIM-2 Study 2X2 Factorial Design (n=2091)
EC
vs
FEC
q3 wks vs q2 wks
*EC-epirubicin 90 mg/m² IV, cyclophosphamide 600 mg/m² IV q 2 or 3 weeks
*T - paclitaxel 175 mg/m² IV 3-hour infusion, every 2 or 3 weeks
*FEC - 5-fluorouracil 600 mg/m² IV, epirubicin 90 mg/m² IV, cyclophosphamide 600 mg/m² IV, q 2 or 3 wks.
Cognetti et al. PSABCS 2013
7
____ FEC
……. EC
p=0.561*
Pro
bab
ility
of
IDFS
(%
)
*STRATIFIED FOR q2/q3
p=0.234 ____ FEC
……. EC
Pro
bab
ility
of
Ove
rall
Surv
ival
(%
)
*STRATIFIED FOR q2/q3
Pro
bab
ility
of
IDFS
(%
)
____ q3 wks
……. q2 wks
p=0.004
*STRATIFIED FOR EC/FEC
Pro
bab
ility
of
Ove
rall
Surv
ival
(%
) N° pts at risk
p=0.001
*STRATIFIED FOR EC/FEC
____ q3 wks
……. q2 wks
____ q3 wks
……. q2 wks
GIM-2: Cognetti et al. PSABCS 2013
p=0.561
Cameron et al. Lancet Oncol 2013
8
Cameron et al. Lancet Oncol 2013
Insert slides from BETH
9
TCH performed as well as TH-FEC arm
BEATRICE and BETH
• First reports of phase III adjuvant trials solely in TNBC and HER2+ breast cancer
• Neither trial showed a benefit
• BEATRICE: DFS at 3 years better than projected in both arms; no significant benefit, HR 0.87 (95% CI 0.72-1.07), but many lower risk N0 patients (subset with significant benefit)
• Await OS analysis when mature, as well as ECOG adjuvant bevacizumab trial
• BETH: no role for bevacizumab in HER2+ BC
• Still lack robust predictive biomarker(s) to select patients for bevacizumab-based therapy
Albain KS. 11th Annual Best of San Antonio – Bench to Bedside 2014
10
Winer E. HER2 Mini-Symposium PSABCS 12/13/2013 www.SABCS.org
von Minckwitz et al. Oncology, January 2012
Incremental Improvement in Pathologic Complete
Remission (pCR) Rates in HER2-Positive Breast Cancer
11
Winer E. HER2 Mini-Symposium PSABCS 12/13/2013 www.SABCS.org
Winer E. HER2 Mini-Symposium PSABCS 12/13/2013 www.SABCS.org
12
Winer E. HER2 Mini-Symposium PSABCS 12/13/2013 www.SABCS.org
Small HER2+ (T<2.0 cm N0)
Tumors Meta-analysis
• Identify a group of patients that could be
excluded from trials evaluating additional
therapy
• Analyze disease-free survival (DFS) &
overall survival (OS) of patients with small
HER2-positive BC treated with
chemotherapy & trastuzumab in the
seminal randomized controlled trials
O’Sullivan et al. PSABCS 2013
13
Trials Included In Small HER2+ Meta-Analysis
Trial No.
HER2+
Timing of
trastuzumab
Duration of
trastuzumab
therapy
Chemo
regimen
Median
follow up
(years)
HERA 5,102 Sequential
1 -2 years
Any – 94% A;
26% A and T
8.0
NCCTG
N9831
3,505 Concurrent
or
sequential
1 year ACT
AC w TH
AC w TH
8.7
NSABP
B31
3,222 Concurrent 1 year ACT
ACTH
9.4
PACS 04 528 Sequential 1 year FECH
DE H
5.0
FinHER 232 Concurrent 9 weeks D+/-HFEC
V+/-HFEC
5.6
O’Sullivan et al. PSABCS 2013
14
Adjuvant Paclitaxel and Trastuzumab (APT)
(Dana Farber Consortium Trial)
HER2+
ER+ or ER-
Node Negative
< 3 cm
Enroll
T
P
T
P
T
P
T
P
T
P
T
P
T
P
T
P
T
P
T
P
T
P
T
P
PACLITAXEL 80 mg/m2 + TRASTUZUMAB 2 mg/kg x 12
T T T T T T T T T T T T T
FOLLOWED BY 13 EVERY 3 WEEK DOSES
OF TRASTUZUMAB (6 mg/kg)*
Planned N=400
*Dosing could alternatively be 2 mg/kg IV weekly for 40 weeks Tolaney et al. PSABCS 2013
Similar DFS for HR+/HR- and for T1a/b vs T1c
15
Tolaney et al. PSABCS 2013
16
APT Trial Results
Chemotherapy Related Amenorrhea (CRA)
• CRA rates at least 50% in most adjuvant trials
• APT trial premenopausal substudy: CRA at 15 months