Schema di chemioterapia da
associare a trastuzumab e
valutazione della risposta
Laura Biganzoli
U.O. Oncologia Medica “Sandro Pitigliani”
Ospedale di Prato
Istituto Toscano Tumori
Caso clinico
•
•
•
•
Donna di 50 anni
ECOG PS0
Nega comorbidita’
Autopalpazione nodulo mammella dx  mammografia:
nodulo QSE di 5 cm, Ln ascellare dx: C5; agobiopsia
mammaria: B5 CDIS -Carcinoma duttale infiltrante G3, ER
50%, PgR40%, Ki67 30%, HER2 3+; RMN lesione
unifocale
• Non fattibile intervento chirurgico conservativo
• TC Torace-addome e scintigrafia ossea = negative per M+;
ECO cuore=N
Opzioni terapeutiche
•
Si propone alla paziente trattamento neoadiuvante
contenente trastuzumab
1.
2.
3.
4.
antraciclina  taxano + trastuzumab
antraciclina + trastuzumab  taxano + trastuzumab
chemioterapia senza antraciclina + trastuzumab
nessuna chemioterapia ma “dual HER2 targeting”
NSABP B-27
Arm A
Arm B
Arm C
ACx4
ACx4
ACx4
Sx
Tx4
Tx4
Sx
Sx
Overall survival
% pCR
Bear et al. J Clin Oncol 2006
13.7
25.6
T, docetaxel
Sx, surgery
p<.001
MDACC trial
Randomized groups
pCR, % (95% CI)
T+FEC (n=19)
T+FEC+H (n=23)
T+FEC+H (n=22)
26.3 (9-51)
65.2 (43-84)
54.5 (32.2-75.6)
T, paclitaxel; H, trastuzumab
Buzdar et al. Clin Cancer Res 2007
Assigned treatment
Randomized study population
NOAH: Phase III, Open-Label Trial of
Neoadjuvant Trastuzumab
Gianni et al. Lancet. 2010
Cardiac safety
MDACC
- No clinical cardiac dysfunction
- Exact binomial 95% CI of the probability
of cardiac failure = 0% to 7.8%
Buzdar et al. Clin Cancer Res 2007
NOHA
Median follow-up 3.2 yrs
Gianni et al. Lancet. 2010
Neo-ALTTO
NeoSphere
pCR rates
Baselga et al. Cancer Res 2010
Gianni et al. Cancer Res 2010
pCR rate in NOHA= 43%
NeoSphere
Gianni et al. Cancer Res 2010
Chang et al.
Chang et al. ASCO 2011
Mia opinione
1.
2.
Chemioterapia contenente antracicline e taxani =
standard
Mancano dati di safety a lungo termine per
somministrate trastuzumab in associazione ad
antracicline
• La paziente e’ stata trattata con AC x 4  docetaxel x 4
+ trastuzumab
• Sottoposta a quadrantectomia + svuotamento del cavo
ascellare. EI: CDIS. Infiltrazione cancerigna di 1/16 ln
esaminati
• Definiamo la risposta come pCR?
1. Si
2. No
• The literature has included several definitions of pCR as well as
several attempts to design a sliding scale of pathologic response in
order to avoid the limitations of a dichotomous endpoint (overly
simplistic– residual disease Δ from near pCR to frank resistance)
Sahoo and Lester. Arch Pathol Lab Med 2009
Definition of pCR
• NSABP B27: Surgical specimens with no invasive
cancer in the breast were considered to be a pathologic
complete response (pCR)
Mazouni et al. J Clin Oncol 2007
Outcome according to the pathological
status of the breast and the axilla
• When there is no residual
invasive cancer in the breast, the
number of involved axillary lymph
nodes is inversely related to survival
(NSABP-B27)
Bear et al. J Clin Oncol 2006
• Patients who convert to nodenegative status after treatment have
excellent survival, even if there is
residual disease (RD) in the breast
Hennessy et al. J Clin Oncol 2005
Neo-ALTTO: pCR and total pCR
Total pCR= breast + axilla
• La risposta al trattamento neoadiuvante
puo’ essere definita pCR
Back up
yes
unk
no