HIV JO Slide Template

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FRANCESCO BOCCARDO
INIBITORI DELLAROMATASI
(back from San Antonio)
Professore Ordinario di Oncologia Medica,
Università di Genova
Direttore Oncologia Medica BIST .Genova
Presidente Nazionale Associazione Italiana
Oncologia Medica
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Decision Points
Initial diagnosis 2-3 years after Tam or AI 5 years after Tam or AI Beyond 10 years?
1
?
?
4
3
?
2
3
?
?
?
4
3
Decision Pointsafter 2-3 yrs of Tam
Initial diagnosis 2-3 years after Tam 5 years after Tam or AI More
IES ABCSG8/ARNO95 ITA
?
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Tamoxifen
?
Aromatase inhibitor
5 years total
10 years total
gt 10 years
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The Lancet 9561533-5, 2007
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The Lancet 9561533-5, 2007
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The Lancet 9561533-5, 2007
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AIOG Metanalysis
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.back from San Antonio 2008 take home
1 There is a clear benefit (including a S
benefit) in switching women already on treatment
with Tam to an AI (anastrozole,exemestane) unless
AI therapy is contraindicated
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Decision Points Initial choice
Initial diagnosis 2-3 years after Tam 5 years after Tam or AI Beyond 10 years?
?
?
ATAC BIG 1-98 monotherapy TEAM 2.75 yr
2
?
?
?
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ATAC100 mos median follow-up , Lancet Oncology
2007
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AIOG Metanalysis
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TEAM trial
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.back from San Antonio 2008 take home
2 Which drug or which patients?
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Predicting the benefit and the risks. Tamoxifen
vs Ais

• Tumor Profile

• Patient Profile

• ERPgR
• HER2
• Recurrence Score
• Cyclin E
• uPA/uPAI-1
• Bcl-2
• ER-beta

• Osteoporosis
• Hypercholesterolemia
• CV risk factors
• Endometrial pathologies
• DVT TE risk factors
• SSRI use
• CYP 19 Genotype
• CYP2D6 Genotype

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• TRANSACT

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• ABCSG 8

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.back from San Antonio 2008 take home 3
Starting with an Ai is a reasonable choice
especially in certain patient subsets (i.e.
PgRneg,HER2 pos,HRScore Node neg,poor
metabolizers of CYP2D6.!)however 1) no major
survival advantge yet 2) No over rate in
selecting patients
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Decision Pointssequencing
Initial diagnosis 2-3 years after Tam or AI 5 years after Tam or AI Beyond 10 years?
1
?
?
4
3
ABCSG8 TEAM 5-yr n.a. yet
?
2
3
BIG-1-98
?
?
?
4
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18491865-792 2922
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Actually received treatment
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Actually received treatment
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Sequencing versus LTZ
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Take home 3
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DOUBLE TRIAL
Switch point
Examestane(3 years)
LTZ/ANA (2 years)
Randomize
Primarysurgery
LTZ/ANA(2 years)
LTZ/ANA(3 years)
Switching period
Sequencing period
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• .back from S. Antonio 2008 Take home 4
• sequencing TAM with an Ai is better
• than TAM alone,but it does not offer major
• advantages vs Ai alone switching from an
• Ai to TAM is possible if required

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Decision Pointsafter 5 yrs of Tam
Initial diagnosis 2-3 years after Tam 5 years after Tam or AI More
NSABP B-14
?
MA.17 ABCSG6a
Tamoxifen
?
Aromatase inhibitor
NSABP B-42
5 years total
10 years total
gt 10 years
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NSABP B-14 No Benefit of Extending Tamoxifen
Beyond 5 Years
DFS
OS
100
100
94
90
90
91
P .07
82
P .03
80
80
78
Percentage of Patients
Percentage of Patients
Placebo Tamoxifen
Placebo Tamoxifen
70
70
60
60
50
50
0
5
7
1
2
4
6
3
0
5
7
1
3
2
4
6
Years
Years

• Tamoxifen demonstrated higher rates of
  endometrial cancer, and more deaths from ischemic
  heart disease and cerebrovascular disease

Fisher B, et al. J Natl Cancer Inst.
200193684-690.
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MA.17 Key Endpoints in Nodal Subgroups

• Preplanned analysis (n 5187)

HR 0.45 (0.27-0.75)
HR 0.63 (0.31-1.27)
HR 1.52 (0.76-3.06)
Node neg
Node neg
Node neg
HR 0.82 (0.57-1.19)
Distant DFS
OS
DFS
HR 0.58 (0.45-0.76)
HR 0.61
Nodepos
Node pos
Node pos
HR 0.61 (0.45-0.84)
HR 0.53 (0.36-0.78)
HR 0.61 (0.38-0.98)
non statistically significant
Goss PE, et al. J Natl Cancer Inst.
2005971262-1271.
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Adjusted HR (PLAC-LET to PLAC) for Efficacy
Outcomes postumblinding
Disease-free survival
Distant disease-free survival
Overall survival
Contralateral breast cancer
0.6
0.53
0.5
p0.05
P .05
0.4
Hazard Ratio
0.31
0.28
0.3
0.23
plt0.0001
P lt .0001
p0.002
P .002
0.2
p0.012
P .012
0.1
0
PLAC-LET to PLAC
Goss PE, et al. SABCS 2005. Abstract 16.
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• back from S.Antonio 2008 Take home 5
• Late switching after 5 yrs of TAM no news

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Decision Pointsafter 5 yrs of AIs
Initial diagnosis 2-3 years after Tam 5 years after Tam or AI More
NSABP B-14
?
MA.17
Tamoxifen
?
Aromatase inhibitor
MA.17-R
NSABP B-42
5 years total
10 years total
gt 10 years
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NSABP B-42 Study Design
Letrozole vs placebo after 5 years not yet
enrolling
Letrozole x 5 yrs
AI x 5 yrs
Placebo x 5 yrs
Tam x 2-3 yrs
AI x 3-2 yrs
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MA.17R Design
Rerandomization (Disease-free)
Letrozole 2.5 mg qd
Letrozole
Placebo qd
5 years early adjuvant
5 years extended adjuvant
Primary endpoint DFS Secondary endpoints OS,
incidence of contralateral breast cancer,
long-term clinical and laboratory safety, overall
QoL, menopausal QoL
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• .back from S. Antonio 2008 Take home 6
• are trials concerning Ai optimal duration still
• prioritary?

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• ZO-FAST

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Immediate Therapy With Zoledronic Acid Prevents
Bone Loss and Improves DFS in Women With Early
Breast Cancer Receiving Letrozole Zometa-Femara
Adjuvant Synergy Trial (ZO-FAST) 36-month
follow-up results of multicenter, randomized
phase III trial1
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• .back from S. Antonio 2008 Take home 7
• the seed and soil theory likely to work data
• from ABCSG 12 confirmed!

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AIs IN THE ADJUVANT SETTING,back from San
Antonio 2008
EARLY SWITCHING 1) the new standard for
the patients already on treatment with
TAM from 2 or
3 yrs 2)
switching from LTZ to TAM after 2-3 yrs possible
if required LATE SWITCHING a reasonable
option for patients at the completion of 5 yrs of
TAM, namely for N pos (no news from San
Antonio) UPFRONT the choice for
the patients who have contraindications to the
use of TAM.
A reasonable choice for the patients at higher
risk of
relapse (HR score) or for whom a suboptimal
response to
TAM might be predicted (CYPD26) cost/benefit
to be defined
in the individual patient (no S advantage on the
average) SEQUENCING 1) no better /no worse
than LTZ 2)
evidence of a significant benefit in respect to
TAM alone
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back from S.Antonio 2008 Take home 8
THANK YOU!