Carcinoma mammario metastaticoCASO CLINICO n.2

Stefania Gori

Oncologia Medica- Perugia

Caso clinico n.2Agosto 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+ IHCSettembre 2001: Programma terapeutico (altrove): CT adiuvante (FECTaxano) seguita da RT Aveva ricevuto 1° ciclo di F600E90C600

Caso clinico n.2Vengono 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 +ZometaTrastuzumabPaclitaxel

Febbraio 2010

RC

Zometa+trastuzumab

Trattamenti

Ottobre 2009

IV stadio

RT femore dx +ZometaTrastuzumabPaclitaxel

Febbraio 2010

RC

Zometa+trastuzumab

Nov 2010

PD

SNCLNOsso

Novembre 2010:RM encefalo T1 con gadolinio

A- Trattamento locale terapia sistemica

B- Terapia sistemica trattamento locale

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?

Dicembre 2010

RT stereotassica su entrambe le lesioni

(dose di riferimento:18 Gy)

Systemic therapy in brain metastases from HER2+ BC:

when?

1-3 brain lesions

Local treatment

Multiple (>3) brain lesions

Systemic therapy

WBRT

The choice of systemic therapy must be tailored on the following factors: Performance Status and previous agents received

Systemic therapy

WBRT

Extracranial disease and ..

Systemic therapy

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)

NR

Sutherland SBJC 2010;102:995

34 YES (94%) YES YES:

35%

RECIST 21% 5.1 mo NR

Huang C ASCO 2010 #1111

26 YES (100%) YES NO RECIST 34% 8.4 mo NR

Metro GAnn Oncol 2011

22 YES (87%) YES NO WHO 32% 5.1 mo 27.9 mo

Lin NU,CCR 2009;15:1452-9

50* YES (100%) YES NO Composita (≥50% vol )

20% 3.6 mo NR

Lin NU,J Neurooncol 2011 online

13 YES (100%) YES NO Composita (≥50% vol )

38% NR NR

Bachelot T,ASCO 2011, # 509

45 NO YES(93%)

NO Composita (≥50% vol )

67% 5.5 mo 91% alive at 6 mo

RETROSPECTIVE STUDIES

PHASE II PROSPECTIVE STUDIES

Lapatinib+Capecitabine (all pts pretreated with CT)

* Optional extension phase after cerebral progression

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

Progression in the brain - 52% -

Progression in extra-CNS +/- CNS sites

- 48% -

Brain metastases in HER2+ breast cancerCauses of death

Systemic therapy in brain metastases from HER2+ BC:

when?

1-3 brain lesions

Local treatment

Multiple (>3) brain lesions

Systemic therapy

WBRT

The choice of systemic therapy must be tailored on the following factors: Performance Status and previous agents received

Systemic therapy

WBRT

Extracranial disease and ..

Systemic therapy

A- Trastuzumab-based therapy

B- Lapatinib +capecitabine

C- Chemotherapy only

2- Quale terapia sistemica?

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

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

•Lapatinib + capecitabine phase II trial- Bachelot ASCO 20111

retrospective study 2

•Lapatinib + capecitabine

phase II trials 3,4; retrospective studies Brain progression after RT

•Trastuzumab-based therapy (?) retrospective data

•Lapatinib + capecitabine phase II trial- Bachelot ASCO 20111

retrospective study 2

Trattamenti

Dic 2010:

RT stereotassicacerebrale

Lapatinib+capecitabina

Nov 2011RC

Marzo 2011 RC

Ottobre 2009

IV stadio

RT femore dx

ZometaTrastuzumab+Paclitaxel

Febbraio 2010

RC

Zometa+trastuzumab

Nov 2010

PD

SNCLNOsso

PET/TC RM encefalo

PET/TC RM encefalo

Novembre 2011

Grazie!