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 (FECTaxano) 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 Ottobre 2009 IV stadio RT femore dx + Zometa Trastuzumab Paclitaxel Febbraio 2010 RC Zometa+ trastuzumab Trattamenti Ottobre 2009 IV stadio RT femore dx + Zometa Trastuzumab Paclitaxel Febbraio 2010 RC Zometa+ trastuzumab Nov 2010 PD SNC LN Osso Novembre 2010: RM encefalo T1 con gadolinio 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) Systemic therapy in brain metastases from HER2+ BC: when? Extracranial disease and .. 1-3 brain lesions Local treatment Systemic therapy Multiple (>3) brain lesions WBRT 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 STUDY N Prior cranial RT Prior trastuzumab Prior Cape (all pts pretreated with CT) Response criteria CNS ORR TTPPFS OS 2.8 mo NR RETROSPECTIVE STUDIES Boccardo F, 138 NR YES ASCO 2008 #1094 YES: 42% Investigatorassessed 18% (median time on study) Capri G, Ann Oncol 2010 Sutherland S 34 YES (94%) YES YES: 35% RECIST 21% 5.1 mo NR 26 YES (100%) YES NO RECIST 34% 8.4 mo NR 22 YES (87%) YES NO WHO 32% 5.1 mo 27.9 mo BJC 2010;102:995 Huang C ASCO 2010 #1111 Metro G Ann Oncol 2011 PHASE II PROSPECTIVE STUDIES Lin NU, 50* YES (100%) YES NO Composita (≥50% vol ) 20% 3.6 mo NR 13 YES (100%) YES NO Composita (≥50% vol ) 38% NR NR 45 NO YES (93%) NO Composita (≥50% vol ) 67% 5.5 mo 91% alive at 6 mo CCR 2009;15:1452-9 Lin NU, J Neurooncol 2011 online Bachelot T, ASCO 2011, # 509 * Optional extension phase after cerebral progression Brain metastases in HER2+ breast cancer Causes of death PRE-Trastuzumab era POST-Trastuzumab era Progression in the brain 46% 60% ns Progression in extra-CNS sites 37% 12% 0.014 Unknown 17% 28% - Progression in the brain - 52% - Progression in extra-CNS +/- CNS sites - 48% - p Park YH, BJC 2009 Bendell JC, Cancer 2003 Systemic therapy in brain metastases from HER2+ BC: when? Extracranial disease and .. 1-3 brain lesions Local treatment Systemic therapy Multiple (>3) brain lesions WBRT 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 Brain metastases in HER2-positive Trastuzumab-pretreated MBC SYSTEMIC THERAPY OPTIONS- Sept 2011 Newly diagnosed brain metastases and no PD at extracranial sites Newly diagnosed brain metastases and PD at extracranial sites •Trastuzumab-based therapy (?) retrospective data •Lapatinib + capecitabine phase II trial- Bachelot ASCO 20111 retrospective study 2 •Lapatinib + capecitabine phase II trial- Bachelot ASCO 20111 retrospective study 2 •Lapatinib + capecitabine Brain progression after RT phase II trials 3,4; retrospective studies 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 Ottobre 2009 Febbraio 2010 Nov 2010 IV stadio RC PD RT femore dx Zometa+ trastuzumab SNC LN Osso Zometa Trastuzumab+ Paclitaxel Dic 2010: RT stereotassica cerebrale Lapatinib+ capecitabina Marzo 2011 Nov 2011 RC RC PET/TC RM encefalo PET/TC RM encefalo Novembre 2011 Grazie!
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