Schema di chemioterapia da associare a trastuzumab e valutazione della risposta

1. 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

2. 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

3. Opzioni terapeutiche • Si propone alla paziente trattamento neoadiuvante contenente trastuzumab • antraciclina taxano + trastuzumab • antraciclina + trastuzumab  taxano + trastuzumab • chemioterapia senza antraciclina + trastuzumab • nessuna chemioterapia ma “dual HER2 targeting”

4. ACx4 ACx4 ACx4 Sx Sx Tx4 Sx Tx4 NSABP B-27 Arm A Arm B Arm C T, docetaxel Sx, surgery % pCR 13.7 25.6 p<.001 Overall survival Bear et al. J Clin Oncol 2006

5. MDACC trial T, paclitaxel; H, trastuzumab Buzdar et al. Clin Cancer Res 2007 Randomized study population

6. NOAH: Phase III, Open-Label Trial of Neoadjuvant Trastuzumab Gianni et al. Lancet. 2010

7. 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

8. Neo-ALTTO NeoSphere pCR rates Baselga et al. Cancer Res 2010 Gianni et al. Cancer Res 2010 pCR rate in NOHA= 43%

9. NeoSphere Gianni et al. Cancer Res 2010 Chang et al. Chang et al. ASCO 2011

10. Mia opinione • Chemioterapia contenente antracicline e taxani = standard • Mancano dati di safety a lungo termine per somministrate trastuzumab in associazione ad antracicline

11. 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? • Si • No

12. 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

14. 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

15. 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 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

16. Neo-ALTTO: pCR and total pCR Total pCR= breast + axilla

17. La risposta al trattamento neoadiuvante puo’ essere definita pCR

18. Back up

20. yes unk no