Schema di chemioterapia da associare a trastuzumab e valutazione della risposta Laura Biganzoli U.O....
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Transcript of Schema di chemioterapia da associare a trastuzumab e valutazione della risposta Laura Biganzoli U.O....
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. antraciclina taxano + trastuzumab
2. antraciclina + trastuzumab taxano + trastuzumab
3. chemioterapia senza antraciclina + trastuzumab
4. nessuna chemioterapia ma “dual HER2 targeting”
ACx4 ACx4 ACx4
Sx Sx
Sx
Tx4
Tx4
NSABP B-27
T, docetaxelSx, surgery
% pCR 13.7 25.6 p<.001
Arm A Arm B Arm C
Bear et al. J Clin Oncol 2006
Ov
era
ll s
urv
iva
l
Randomized groups Assigned treatment
T+FEC (n=19) T+FEC+H (n=23) T+FEC+H (n=22)
pCR, % (95% CI) 26.3 (9-51) 65.2 (43-84) 54.5 (32.2-75.6)
MDACC trial
Randomized study population
T, paclitaxel; H, trastuzumab
Buzdar et al. Clin Cancer Res 2007
NOAH: Phase III, Open-Label Trial of Neoadjuvant Trastuzumab
Gianni et al. Lancet. 2010
Cardiac safety
- No clinical cardiac dysfunction
- Exact binomial 95% CI of the probability of cardiac failure = 0% to 7.8%
- No clinical cardiac dysfunction
- Exact binomial 95% CI of the probability of cardiac failure = 0% to 7.8%
MDACC
NOHA
Gianni et al. Lancet. 2010
Buzdar et al. Clin Cancer Res 2007
Median follow-up 3.2 yrs
Neo-ALTTO NeoSphere
pCR rates
pCR rate in NOHA= 43%Baselga et al. Cancer Res 2010 Gianni et al. Cancer Res 2010
NeoSphere
Chang et al.
Gianni et al. Cancer Res 2010
Chang et al. ASCO 2011
Mia opinione
1. Chemioterapia contenente antracicline e taxani = standard
2. 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
• When there is no residual invasive cancer in the breast, the number of involved axillary lymph nodes is inversely related to survival (NSABP-B27)
• Patients who convert to node-negative status after treatment have excellent survival, even if there is residual disease (RD) in the breast
Hennessy et al. J Clin Oncol 2005
Bear et al. J Clin Oncol 2006
Outcome according to the pathological status of the breast and the axilla
Neo-ALTTO: pCR and total pCR
Total pCR= breast + axilla
• La risposta al trattamento neoadiuvante puo’ essere definita pCR
Back up
no
yesunk