Carcinoma mammario metastatico CASO CLINICO n.2 Stefania Gori Oncologia Medica- Perugia

Caso clinico n.2 Agosto 2009: Donna di anni 37 anni, premenopausa, operata altrove di quadrantectomia mammaria Sx + dissezione ascellare per ca. duttale infiltrante pT2 pN3(20LN+/24) M0; STADIO IIIC G3 ER=0%, PgR=0% Ki67=60% HER2= 3+ IHC Settembre 2001: Programma terapeutico (altrove): CT adiuvante (FECTaxano) seguita da RT Aveva ricevuto 1° ciclo di F600E90C600

Caso clinico n.2 Vengono richiesti: RM encefalo con gadolinio: negativa PET /TC total body (9 ottobre 2009): metastasi LN mediastinici metastasi ossee: - sterno e collo femore dx IV STADIO

Trattamenti IV stadio RC Ottobre 2009 RT femore dx + Zometa Trastuzumab Paclitaxel Febbraio 2010 RC Zometa+ trastuzumab

Trattamenti IV stadio RC PD Ottobre 2009 RT femore dx + Zometa Trastuzumab Paclitaxel Febbraio 2010 RC Zometa+ trastuzumab Nov 2010 PD SNC LN Osso

Novembre 2010: RM encefalo T1 con gadolinio

A- Trattamento locale terapia sistemica 1- Metastasi cerebrali di 6 e 13 mm di diametro (centro semiovale e corteccia frontale dx) asintomatiche, in pt con progressione extracranica asintomatica (ossea e linfonodale). Quale sequenza di trattamento? A- Trattamento locale terapia sistemica B- Terapia sistemica  trattamento locale

Dicembre 2010 RT stereotassica su entrambe le lesioni (dose di riferimento:18 Gy)

when? Systemic therapy in brain metastases from HER2+ BC: Extracranial disease and .. 1-3 brain lesions Multiple (>3) brain lesions Local treatment WBRT Systemic therapy Systemic therapy Systemic therapy WBRT The choice of systemic therapy must be tailored on the following factors: Performance Status and previous agents received

Lapatinib+Capecitabine (all pts pretreated with CT) STUDY N Prior cranial RT Prior trastuzumab Prior Cape Response criteria CNS ORR TTP- PFS OS Boccardo F, ASCO 2008 #1094 Capri G, Ann Oncol 2010 138 NR YES YES: 42% Investigator-assessed 18% 2.8 mo (median time on study) Sutherland S BJC 2010;102:995 34 YES (94%) 35% RECIST 21% 5.1 mo Huang C ASCO 2010 #1111 26 YES (100%) NO 34% 8.4 mo Metro G Ann Oncol 2011 22 YES (87%) WHO 32% 27.9 mo Lin NU, CCR 2009;15:1452-9 50* Composita (≥50% vol ) 20% 3.6 mo J Neurooncol 2011 online 13 38% Bachelot T, ASCO 2011, # 509 45 (93%) 67% 5.5 mo 91% alive at 6 mo RETROSPECTIVE STUDIES PHASE II PROSPECTIVE STUDIES * Optional extension phase after cerebral progression

Brain metastases in HER2+ breast cancer Causes of death PRE-Trastuzumab era POST-Trastuzumab era p Park YH, BJC 2009 Progression in the brain 46% 60% ns Progression in extra-CNS sites 37% 12% 0.014 Unknown 17% 28% - Bendell JC, Cancer 2003 52% Progression in extra-CNS +/- CNS sites 48% Park: 14/42 pts trattate con trastuzumab DOPO meta cerebri (=33%) Bendell : 21% 11

when? Systemic therapy in brain metastases from HER2+ BC: Extracranial disease and .. 1-3 brain lesions Multiple (>3) brain lesions Local treatment WBRT Systemic therapy Systemic therapy Systemic therapy WBRT The choice of systemic therapy must be tailored on the following factors: Performance Status and previous agents received

2- Quale terapia sistemica? A- Trastuzumab-based therapy B- Lapatinib +capecitabine C- Chemotherapy only

SYSTEMIC THERAPY OPTIONS- Sept 2011 Brain metastases in HER2-positive Trastuzumab-pretreated MBC SYSTEMIC THERAPY OPTIONS- Sept 2011 Newly diagnosed brain metastases and no PD at extracranial sites Trastuzumab-based therapy (?) retrospective data Lapatinib + capecitabine phase II trial- Bachelot ASCO 20111 retrospective study 2 Newly diagnosed brain metastases and PD at extracranial sites Lapatinib + capecitabine phase II trial- Bachelot ASCO 20111 retrospective study 2 Lapatinib + capecitabine phase II trials 3,4; retrospective studies Brain progression after RT 1.Bachelot T, ASCO 2011 #505; 2.Metro G, Gori S, Ann Oncol 2011; 3.Lin NU, Clin Cancer Res 2009;4.Lin NU, J Neurooncol 2011 online

Trattamenti RC IV stadio RC PD Nov 2011 Ottobre 2009 RT femore dx Zometa Trastuzumab+ Paclitaxel Febbraio 2010 RC Zometa+ trastuzumab Nov 2010 PD SNC LN Osso Dic 2010: RT stereotassica cerebrale Lapatinib+ capecitabina Marzo 2011 RC PET/TC RM encefalo PET/TC RM encefalo

Novembre 2011

Grazie!