Associazione Trastuzumab e chemioterapia nel carcinoma

Innovazioni terapeutiche in Oncologia Medica
Cagliari 23/24 Giugno 2005
Associazione Trastuzumab e chemioterapia
nel carcinoma mammario metastatico e
localmente avanzato. Nostra casistica.
Carlo Floris
Oncologia Medica II
Cagliari
HER2 Protein Overexpression Associated with Poor
5
Prognosis and Shortened Survival
‹
‹
—
In retrospective studies, Approximately 25%
of breast cancers are HER2-positive1
HER2 was found to be associated with6-9
Shortened survival6,7
8
— More rapid tumor progression
— Increased relapse rate; shorter time to
relapse6,7
9
— Poor responses to standard therapies
Herceptin: Humanized Anti-HER2
Antibody
‹
‹
‹
Targets HER2 oncoprotein,
which occurs in
approximately 25% of
patients with breast cancer1
High affinity (Kd = 5 nM)
and specificity2,3,4
95% human, 5% murine
—
—
Decreased potential for
immunogenicity3
Increased potential for
recruiting immune effector
mechanisms4
Herceptin chemotherapy
combinations: summary
®
„
Several Herceptin combination regimens are active
®
„
„
„
high RRs
favourable safety profiles
Herceptin is FDA approved for the treatment of women
with HER2-driven metastatic breast cancer2
„
„
First-line in combination with paclitaxel
Second-line as a single agent
„
To date, no direct comparison has been made to
establish the best first-line combination strategy
„
Optimal therapy may differ depending on patient and
tumour characteristics
Mean combination index values
for
®
chemotherapeutic drug/Herceptin combinations in
vitro
Combination
index
p value
0.34
<0.0001
Synergy
Docetaxel2
0.41±1.37
0.001
Synergy
Cisplatin 2
0.56±0.15
0.001
Synergy
Epirubicin 2
0.75±0.1
0.057
Addition
Doxorubicin 2
1.16±0.18
0.13
Addition
Paclitaxel2
0.91±0.23
0.21
Addition
5'-dFUrd 3*
1.1±0.2
Drug
Vinorelbine 1
Not specified
Interaction
Addition
*5'-dFUrd is a metabolite of Xeloda®; Herceptin® plus Xeloda® demonstrates additive
activity in vivo3
1Konecny G, et al. Breast Cancer Res Treat 1999;57:114 (Abstract 467)
2Pegram M, et al. Oncogene 1999;18:2241–51
3Fujimoto-Ouchi K, et al. Cancer Chemother Pharmacol 2002;49:211–16
Caratteristiche delle pazienti
„
„
„
„
„
„
„
Pazienti trattate
Eta mediana
Range
ECOG PS 0-1
Pre/Post menopausa
ER-/ER+
HER 3+/FISH+
66
49
30-75
75%
33/33
28/38
54/12
Sedi di metastasi
„
„
„
„
Visceri
Osso
Loco-regionale
Encefalo
37 (56%)
12 (18.1)
9 (13.6)
8 (12.1)
Precedenti terapie
„
„
„
„
„
Mastectomia radicale
Quadrantectomia
Non operate
32
21
13
Precedente antraciclina
Non antraciclina
57 (86%)
9 (14%)
Terapia
„
I linea
II linea
46
20
„
H+Taxano
52
Taxolo
„ Taxotere
42
10
„
„
„
H + Vinorelbina
14
Schedula
„
Paclitaxel
„
„
Docetaxel
„
„
100 mg/mq q 21
Vinorelbina
„
„
175 mg/mq q 21
25 mg/mq q w
Herceptin
„
„
4 mg/Kg 1^ sett
2 mg/Kg sett. succ.
„
Prevenzione emesi
Valutazione cardiologica: FE
„
Tollerabiltà discreta
„
RR
TTP
„
„
Valutazione complessiva
„
Pazienti trattate
Pazienti valutabili
„
OR
„
CR
„ PR
„
„
„
SD
PD
38 (61.2%)
2 (3.2%)
36 (58%)
13 (20.9%)
11 (17.7%)
66
62
Risposta in base alla sede di
metastasi
OR
Loco-regionale 75 %
(8)
Osso
50 %
(12)
Visceri
52.9 %
(34)
Encefalo
100 %
(RT ?)
(8)
CR
PR
SD
PD
0
6
0
2
0
6
3
3
2
16
9
7
0
8
0
0
Risposta in base alla sede di
metastasi
100
90
80
70
60
50
40
30
20
10
0
OR
PR
CR
Loc-reg
Visceri
Osso
Encefalo
Risposta in base ai recettori
(ER / PR)
„
Recettori positivi (38)
„
„
„
PR
(52.6%)
CR
(3.5%)
20
1
„
PR
(53.5%)
CR
(2.6%)
50
PR
40
30
Recettori negativi (28)
„
60
15
20
10
0
1
CR
Re+
Re-
Valutazione per schema di terapia
H+T (46)
H+V (16)
OR
27 (58.6 %)
11 (68.7 %)
CR
1 (2.1 %)
1 (6.2 %)
PR
26 (56.5 %)
10 (62.5 %)
SD
11 (23.9 %)
2 (12.5 %)
PD
8 (17.3 %)
3 (18.7 %)
Valutazione per schema di terapia
70
60
50
40
H+T
H+V
30
20
10
0
OR
CR
PR
SD
PD
TTP (mediana)
„ TTP
7 mesi (1-34)
„ H+V
9 mesi
„ H+T
6 mesi
Conclusioni
L’associazione Trastuzumab –
chemioterapia possiede una buona attività
antitumorale nelle pazienti con carcinoma
mammario localmente avanzato o
metastatico
„ Risposte migliori nelle localizzazioni
viscerali
E’ ipotizzabile una maggiore percentuale di
risposte con l’utilizzo in fasi più precoci
„
„
®
Duration of therapy with Herceptin ?
„
Optimal clinical benefit was achieved when Herceptin® was
given long term (at least until progression)
„
No additional safety concerns were identified with
long-term use in metastatic disease
„
Tumor control post-surgery
„
Continuous Herceptin® therapy to complete 1 year
of treatment is consistent with the adjuvant trials
Æ Herceptin® should be continued up to 52 weeks
post-surgery in patients who achieved CR, PR or SD