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