1. Biologika bei onkologischen Erkrankungen älterer Menschen
Österr. Gesellschaft für Geriatrie und Gerontologie
BIOLOGIKA IN DER GERIATRIE
17. Jänner Wien
Biologika bei onkologischen Erkrankungen älterer Menschen
Prof. Günther Steger
Medizinische Universität Wien

4. Pivotal phase III trial – Trastuzumab in combination with chemotherapy
Design and enrolment
Metastatic breast cancer
HER2 overexpression
No prior CT for MBC
Measurable disease
KPS ³60%
Eligible patients (n=469)
No prior anthracyclines
Prior anthracyclines
Trastuzumab + AC
(n=143) AC
(n=138)
Trastuzumab + Paclitaxel
(n=92)
Paclitaxel
(n=96)
AC = doxorubicin/epirubicin + cyclophosphamide

5. Overall survival – HER2 3+ patients
1.0
0.9
0.8
0.7
0.6
0.5
0.4
0.3
0.2
0.1
0.0
Trastuzumab + CT
CT alone
p<0.05
Probability of survival 20 29
Time (months)

6. Docetaxel +/- Trastuzumab Overall Survival
1.0
0.8
0.6
0.4
0.2
Trastuzumab + docetaxel
Docetaxel alone
Estimated probability
Median overall survival increased from 22.1 months in the docetaxel-alone arm to 30.5 months (p=0.0062) in the combination arm. This is a statistically significant difference and means that patients in the Herceptin® plus docetaxel arm survived on average 8.4 months longer than those in the docetaxel-alone arm. This difference is seen despite the fact that approximately 48% of patients in the docetaxel arm crossed over to receive Herceptin® at disease progression, which reduces the difference in survival seen between the two arms.
p=0.0062
22.1
30.5
Months
8.4 months
Intent-to-treat population, 12-month cut-off Documented crossover = 48%

7. Trastuzumab Treatment in Multiple Lines

8. Adjuvant Treatment: Risks and Benefits
100
No benefit
Death despite
therapy
Optimization of
therapies 80
Benefit 60
No benefit
Survival without
therapie
% of surviving patients
Characterization
of predicitive factors 40
Adjuvant Therapy
Control 20
Jahre

9. Adjuvant Treatment: Risks and Benefits
100
Optimization of
therapies
No benefit
Death despite
therapy 80
Benefit 60
% of surviving patients 40
Characterization
of predicitive factors
No benefit
Survival without
therapie
Adjuvant Therapy
Control 20
Jahre

10. Adjuvant Trastuzumab Trials
HERA
NSABP B-31
NCCTG N9831
BCIRG 006
FinHer
No. patients
5090
2030
3505
3222
232a
Reference
Piccart-Gebhart et al, Smith et al, 20072
Romond et al, 20053
Slamon et al, 20064
Joensuu et al, 20065
aHER2-positive subgroup
1. Piccart-Gabhart M et al. N Engl J Med 2005;353(16):1659–72; 2. Smith I et al. Lancet 2007;369:29–36; 3. Romond EH et al. N Engl J Med 2005;353(16):1673–84; 4. Slamon D et al. SABCS 2006;Abstract 52; 5. Joensuu H et al. N Engl J Med. 2006;354:809-20

11. Adjuvant Trastuzumab Trials: Summary of DFS data to date
Median follow-up
HERA1 (n=5090)
2 years
Combined analysis2 (n=3351)
2 years
BCIRG 006 AC–DH3 (n=1074)
3 years
BCIRG 006 DCarboH3 (n=1075)
3 years
FinHer VH/DHa4 (n=232)
3 years 1 2
Favours Herceptin
Favours no Herceptin HR
aRFS
1. Smith I et al. Lancet 2007;369:29–36; 2. Romond EH et al. N Engl J Med 2005;353(16):1673–84; 3. Slamon D et al. SABCS 2006;Abstract 52; 4. Joensuu H et al. N Engl J Med. 2006;354:809-20

12. Adjuvant trastuzumab trials: summary of OS data to date
Median follow-up
HERA Herceptin 1 year arm1
2 years
Combined analysis2
2 years
BCIRG 006 AC–DH3
3 years
BCIRG 006 DCarboH3
3 years
FinHer VH/DH4
p=NS
3 years 1 2
Favours Herceptin
Favours no Herceptin HR
NS, not significant
1. Smith I et al. Lancet 2007;369:29–36; 2. Romond EH et al. N Engl J Med 2005;353(16):1673–84; 3. Slamon D et al. SABCS 2006;Abstract 52; 4. Joensuu H et al. N Engl J Med. 2006;354:809-20

14. SAFETY ANALYSIS POPULATION
Cardiotoxicity
Observation
N=1736
1 year trastuzumab
N=1677
Decrease by  10 EF points and LVEF < 50%
2.2 %
7.1 %
0 %
(95% CI: )
0.5%
(95% CI: )
Same LVEF criteria
and symptomatic CHF NYHA class III/IV, confirmed by cardiologist
Cardiac death
0.1% 0%

16. DFS BENEFIT IN SUBGROUPS HR: 1 year trastuzumab vs observation
Hazard
Hazard
ratio
ratio n n
All
All
3387
3387
0.54
0.54
Nodal
Nodal
status
status
Any, neo
Any, neo - -
adjuvant chemotherapy
adjuvant chemotherapy
358
358
0.53
0.53
0 pos, no neo
0 pos, no neo - -
adjuvant chemotherapy
adjuvant chemotherapy
1100
1100
0.52
0.52 1 1 - -
3 pos, no neo
3 pos, no neo - -
adjuvant chemotherapy
adjuvant chemotherapy
972
972
0.51
0.51  
4 pos, no neo
4 pos, no neo - -
adjuvant chemotherapy
adjuvant chemotherapy
953
953
0.53
0.53
Adjuvant chemotherapy regimen
Adjuvant chemotherapy regimen
No anthracycline or taxane
No anthracycline or taxane
203
203
0.64
0.64
Anthracycline, no taxane
Anthracycline, no taxane
2307
2307
0.43
0.43
Anthracycline + taxane
Anthracycline + taxane
872
872
0.77
0.77
Receptor status/endocrine therapy
Receptor status/endocrine therapy
Negative
Negative
1674
1674
0.51
0.51
Pos + no endocrine therapy
Pos + no endocrine therapy
467
467
0.49
0.49
Pos + endocrine therapy
Pos + endocrine therapy
1234
1234
0.68
0.68
Age group
Age group
<35 yrs
<35 yrs
251
251
0.47
0.47 35 35 - -
49 yrs
49 yrs
1490
1490
0.52
0.52 50 50 - -
59 yrs
59 yrs
1091
1091
0.53
0.53  
60 yrs
60 yrs
549
549
0.70
0.70
Region
Region
Europe, Nordic, Canada, SA, Aus, NZ
Europe, Nordic, Canada, SA, Aus, NZ
2430
2430
0.58
0.58
Asia Pacific, Japan
Asia Pacific, Japan
405
405
0.42
0.42
Eastern Europe
Eastern Europe
364
364
0.31
0.31
Central + South America
Central + South America
188
188
0.90
0.90
Favors
Favors 1 1
Favors
Favors 2 2
trastuzumab
trastuzumab
observation
observation

17. Trastuzumab provides DFS benefit across a range of ages
N9831 / B-31
<40 years
40-49 years
50-59 years
≥60 years
0.0
0.5
1.0
1.5
2.0
2.5
Favours Herceptin
Favours no Herceptin
References
Perez EA et al. J Clin Oncol (Meeting Abstracts) 2007; 25: 6s, abs 512.
Smith IE et al. Lancet 2007; 369: HR
Perez et al 2007; Smith et al 2007 18

18. Trastuzumab treatment in elderly patients with advanced breast cancer: results from a large observational study
Jackisch et al. Poster #3144
SABCS 2008

19. METHODEN I

20. METHODEN II

21. Gesamtüberleben: Vergleich der Patienten unter 65 und über 65

22. Zeit bis zur Progression

23. Sicherheitsprofil bei älteren Patienten

24. Konklusionen - Effektivität

25. Konklusionen - Toxizität

26. Gesamtkonklusionen

27. }30% Breast Cancer Mortality in Europe
1.2
}30%
Standardized Mortality Rate
0.8
Auch „elderly patients“ haben das
Recht auf diesen Survival-Benefit
0.4