Aggiornamenti
scientifici
di NAB-paclitaxel
nel MBC in terapia
di combinazione
Studi con Abraxane in combinazione con schedula
settimanale: dati di efficacia e tollerabilità
Jackisch C et al., Breast Care (Basel). 2012 Apr;7(2):137-143
Phase II Trial of Weekly NAB-paclitaxel in
Combination With Gemcitabine in
Patients With Metastatic Breast Cancer
V. Roy, B. R. LaPlant, G. G. Gross,
C. L. Bane, F. M. Palmieri,
on behalf of the North Central Cancer Treatment Group
Roy V et al. Ann Oncol. 2009;20(3):449-453.
NAB-paclitaxel più gemcitabina:
disegno dello studio
• This was an open-label, multicenter phase II study conducted through
the North Central Cancer Treatment Group
NAB-Paclitaxel
125 mg/m2
Days 1 and 8 every 21 days
IV, intravenous; MBC, metastatic breast cancer.
Gemcitabine
1000 mg/m2
Days 1 and 8 every 21 days
Roy V et al. Ann Oncol. 2009;20(3):449-453.
NAB-paclitaxel più gemcitabina: efficacia del
trattamento di prima linea nelle donne con MBC
Outcome (N = 50)
Number of administered cycles, median (range)
ORRa (≥ PR), n (%; 95% CI)
Value
7 (1-17)
25 (50; 36-64)
CR, n (%)
4 (8)
PR, n (%)
20 (42)
Duration of response in months, median (95% CI)
6.9 (5.7, NR)
PFS in months, median (95% CI)
7.9 (5.4-10)
OS in months, median (95% CI)
NR
6-month PFS, % (95% CI)
60 (48-76)
6-month OS, % (95% CI)
92 (85-100)
a
Overall confirmed response.
CI, confidence interval; CR, complete response; MBC, metastatic breast
cancer; NR, not reached; ORR, overall response rate; OS, overall survival;
PFS, progression-free survival; PR, partial response.
Roy V et al. Ann Oncol. 2009;20(3):449-453.
Phase II Multicenter Trial of NAB-paclitaxel
and Capecitabine in First-Line Treatment of
Patients with Metastatic Breast Cancer
Schwartzberg et al. Clin Breast Cancer. 2012 Apr;12(2):87-93
NAB-paclitaxel e capecitabina:
disegno dello studio
Purpose: A single arm, multi-center phase II trial to determine efficacy of
NAB-Paclitaxel + capecitabine as first line treatment of MBC patients
(HER2-)
– N = 50
– Patients with ECOG PS 0-2, HER2-, adequate organ function
– Cycles of 21 days until disease progression or dose-limiting toxicity
NAB-paclitaxel
125 mg/m2
IV over 30 min
Days 1 and 8 q3w without
premedication
Capecitabine 825 mg/m2
Orally bid
Days 1-14 q3w
Endpoints
• Primary: ORR
• Secondary: PFS, OS, safety
bid, twice daily; IV, intravenous; MBC,
metastatic breast cancer; q3w, every 3
weeks.
Schwartzberg et al. Clin Breast Cancer. 2012 Apr;12(2):87-93
NAB-paclitaxel e capecitabina:
tassi di risposta
Outcome (N = 46)
n (%)
ORR
CR
PR
28 (61)
2 (4)
26 (57)
SD
10 (22)
PD
8 (17)
Note: 4 of the 50 patients not evaluable for response.
CR, complete response; MBC, metastatic breast cancer; ORR, overall
response rate; PD, progressive disease; PR, partial response; SD,
stable disease.
Schwartzberg et al. Clin Breast Cancer. 2012 Apr;12(2):87-93
NAB-paclitaxel e capecitabina:
Progression Free Survival
The red line indicates product limit estimate of survival curve and circles indicate a
censored observation
Schwartzberg et al. Clin Breast Cancer. 2012 Apr;12(2):87-93
NAB-paclitaxel e capecitabina:
Overall Survival
The red line indicates product limit estimate of survival curve and circles indicate a
censored observation
NAB-paclitaxel e lapatinib
nel MBC HER2+: risultati
NAB-paclitaxel e lapatinib
nel MBC HER2+: risultati
STUDIO GOIM
NAB-paclitaxel e Capecitabina in MBC
14
STUDIO GOIM - NAB-paclitaxel e capecitabina in
MBC - Disegno dello studio
A MULTICENTER PHASE II TRIAL OF NAB-PACLITAXEL AND
CAPECITABINE AS FIRST LINE TREATMENT IN HER-2 NEGATIVE
METASTATIC BREAST CANCER (MBC)
– N = fino a 94
– Pazienti con ECOG PS 0-1, HER2-, inclusi TN, adeguata funzionalità d’organo
– 6 cicli (+ 2 a discrezione del clinico)
nab paclitaxel
150 mg/m2
IV in 30 min
GG 1 e 8 q3w
senza premedicazione
Capecitabina 825 mg/m2
Orale 2 volte al giorno
GG 1-14 q3w
Endpoints
• Primario: ORR, PFS
• Secondari: OS, safety
bid, twice daily; IV, intravenous; MBC, metastatic breast cancer; q3w, every 3 weeks.
EUDRACT 000393-35
Phase II Trial of Weekly NAB-paclitaxel With
Carboplatin and Trastuzumab as First-Line
Therapy for Women
With HER2-Overexpressing
Metastatic Breast Cancer
A. K. Conlin, A. D. Seidman, A. Bach, D. Lake,
B. M. Dickler, G. D’Andrea, T. Traina, M. Danso,
A. M. Brufsky, M. Saleh, A. Clawson, C. A. Hudis
Conlin AK et al. Clin Breast Cancer. 2010;10(4):281-287.
NAB-paclitaxel, carboplatino e trastuzumab
nel MBC HER2+: schema terapeutico
AUC, area under the curve; HER2, human epidermal growth factor
receptor2; MBC, metastatic breast cancer; wk, week.
Conlin AK et al. Clin Breast Cancer. 2010;10(4):281-287.
NAB-paclitaxel, carboplatino e trastuzumab nel
MBC HER2+: risultati di efficacia
Confirmed responses (N = 32)
Value
ORR (CR + PR), n (%; 95% CI)
20 (63; 45.7-79.3)
CR, n (%)
3 (9)
PR, n (%)
17 (53)
SD ≥ 16 weeks, n (%)
6 (19)
Clinical benefit (CR + PR + SD ≥ 16 weeks), n (%)
26 (81)
• Median response duration: 17.8 months (95% CI, 15.9-37.0)
• Median PFS: 16.6 months (95% CI, 7.5-26.5)
• Thirty-two patients treated
– Seventeen treated solely on original regimen
– Three switched from original to revised regimen
– Twelve treated only on revised regimen
CI, confidence interval; CR, complete response; HER2, human epidermal
growth factor receptor 2; MBC, metastatic breast cancer; ORR, overall
response rate; PR, partial response; SD, stable disease.
Conlin AK et al. Clin Breast Cancer. 2010;10(4):281-287.
Conclusioni
• NAB-paclitaxel viene impiegato oggi con schedula trisettimanale (260 mg/m2),
ma le evidenze attualmente disponibili giustificano il suo impiego anche in
somministrazione settimanale (150, 125, 100 mg/m2 )
• La scelta della schedula deve essere guidata dalle terapie precedenti per la
malattia metastatica, dalle condizioni generali della paziente e dall’eventuale
combinazione con altri farmaci (chemioterapici e/o biologici)*
• I dati clinici supportano il trattamento con NAB-paclitaxel in MBC dalla 1° linea
in poi, anche per le pz pre-trattate con taxani in adiuvante, ricadute o refrattarie
• La neuropatia sensoriale, che si manifesta in genere tardivamente nel corso del
trattamento con NAB-paclitaxel, può essere gestita con riduzione/interruzione di
dose e migliora rapidamente
* Le linee-guida tedesche dell’AGO (Working Group on Breast Cancer) raccomandano la CT con singolo
agente se il paziente progredisce lentamente e non soffre di sintomi considerevoli e di metastasi acute che
ne minacciano la sopravvivenza