Transcript Trastuzumab - Cancer de Mama

TRATAMIENTO PRECOZ
ESTRATEGIAS CON TERAPIAS BIOLÓGICAS
Miquel Àngel Seguí Palmer
ESTRATEGIAS CON TERAPIAS BIOLÓGICAS
Tratamientos orientados a una diana molecular diferenciada como es el
Her2 (Trastuzumab y Lapatinib)
Tratamientos sin un claro grupo de pacientes con una diana específica
(Bevacizumab y ácido Zoledrónico)
Tratamientos que ya tienen un peso específico y están integrados en la
práctica habitual (Trastuzumab)
Tratamientos que tienen algunos resultados prometedores en estudios
de adyuvancia (ácido Zoledrónico) pero todavía precisan de más
información .
Tratamientos que están en fase de estudio y a la los que todavía les
queda un largo recorrido antes de formar parte de las estrategias
habituales en adyuvancia (Lapatinib y Bevacizumab).
TRASTUZUMAB
TRASTUZUMAB
Indicación del fármaco en los tumores de
teórico buen pronóstico
TRASTUZUMAB
Cuando se analiza lo que pasa en el “mundo real”,
aproximadamente la mitad de las pacientes Her2 + no
reciben tratamiento adyuvante con Trastuzumab
TRASTUZUMAB
TRASTUZUMAB
A retrospective cohort of 367, grade 1 or 2, node
negative patients was analysed to assess the impact of
HER2 status (Herceptest 3+ or FISH positive) on
survival in this otherwise very good prognostic group.
The patients were diagnosed between 1980- 2002, had
full follow-up and were 89% ER positive, with 72%
smaller than 20mm. 10% received chemotherapy and
91% received endocrine therapy.
TRASTUZUMAB
TRASTUZUMAB
TRASTUZUMAB
TRASTUZUMAB
Recurrence Free Survival
by HER2 Status
Recurrence Free Survival by
breast cancer subtype
TRASTUZUMAB
Multivariable Models
Conclusions
•HER2 positivity is a powerful negative prognostic factor for
patients with tumors 1 cm or less (HR: 2.7, 95% CI 1.44-5.0).
•Systemic treatment with anti-HER2 directed therapies should be
strongly considered in this population.
•Clinical trials should include this group of patients.
TRASTUZUMAB
Datos de cardiotoxicidad de una serie de 54 pacientes
Her2+ tratadas con trastuzumab fuera de un ensayo clínico
TRASTUZUMAB
Twelve patients (22.2%) interrupted their
trastuzumab therapy. Eleven (20.4%) due
to an asymptomatic drop in LVEF of >10%
while one patient (1.9%) experienced a
symptomatic cardiac toxicity requiring
treatment.
The mean number of cycles completed
prior to discontinuation was 2.75 and the
mean drop in LVEF was 17.6%.
•Significant decline in LVEF after 12
weeks on trastuzumab (p = 0.003)
•LVEF values remained stable thereafter
Two patients restarted and completed their
trastuzumab therapy at a later date.
TRASTUZUMAB
Datos preliminares de toxicidad de un estudio fase II de gran tamaño con
el esquema TC con trastuzumab concomitante en pacientes Her2+
TRASTUZUMAB
ÁCIDO ZOLEDRÓNICO
ABCSG - 12
ÁCIDO ZOLEDRÓNICO
ÁCIDO ZOLEDRÓNICO
ÁCIDO ZOLEDRÓNICO
The effect of zoledronic acid on aromatase inhibitor associated bone loss in
postmenopausal women with early breast cancer receiving letrozole: 36 months
follow-up of ZO-FAST
H. Eidtmann, N.Bundred, R. De Boer, A. Llombart, N. Davidson, P. Neven, G. von Minckwitz, J. Miller,
N. Schenk, and R.Coleman on behalf of the ZO-FAST Trialists’ Group
ÁCIDO ZOLEDRÓNICO
The effect of zoledronic acid on aromatase inhibitor associated bone loss in
postmenopausal women with early breast cancer receiving letrozole: 36 months
follow-up of ZO-FAST
H. Eidtmann, N.Bundred, R. De Boer, A. Llombart, N. Davidson, P. Neven, G. von Minckwitz, J.
Miller, N. Schenk, and R.Coleman on behalf of the ZO-FAST Trialists’ Group
ÁCIDO ZOLEDRÓNICO
The effect of zoledronic acid on aromatase inhibitor associated bone loss in
postmenopausal women with early breast cancer receiving letrozole: 36 months
follow-up of ZO-FAST
H. Eidtmann, N.Bundred, R. De Boer, A. Llombart, N. Davidson, P. Neven, G. von Minckwitz, J.
Miller, N. Schenk, and R.Coleman on behalf of the ZO-FAST Trialists’ Group
ÁCIDO ZOLEDRÓNICO
The effect of zoledronic acid on aromatase inhibitor associated bone loss in
postmenopausal women with early breast cancer receiving letrozole: 36 months
follow-up of ZO-FAST
H. Eidtmann, N.Bundred, R. De Boer, A. Llombart, N. Davidson, P. Neven, G. von Minckwitz, J.
Miller, N. Schenk, and R.Coleman on behalf of the ZO-FAST Trialists’ Group
ÁCIDO ZOLEDRÓNICO
ÁCIDO ZOLEDRÓNICO
LAPATINIB
Dose-dense doxorubicin and cyclophosphamide followed by weekly paclitaxel with trastuzumab and lapatinib in
HER2/neu-positive breast cancer is not feasible due to excessive diarrhea: updated results.
Dang C, Lin N, Moy B, Come S, Lake D, Theodoulou M, Troso-Sandoval T, Dickler M, Gorsky M, D'Andrea G, Modi S, Seidman A, Drullinsky P, Partridge A, Schapira L, Wulf G, Gilewski T, Atieh D, Mayer E, Isakoff S, Sugarman S, Fornier M, Traina T, Bromberg J, Currie V, Robson M,
Burstein H, Overmoyer B, Ryan P, Kuter I, Younger J, Schumer S, Tung N, Zarwan C, Schnipper L, Chen C, Winer E, Norton L, Hudis C Memorial Sloan-Kettering Cancer Center, New York, NY; Dana Farber Cancer Institute, Boston, MA; Massachusetts General Hospital, Boston, MA;
Beth Israel Deaconess Medical Center, Boston, MA
From March 2007 to April 2008, we enrolled 95 pts. Median age was 45 years
(range, 28-73). At a med follow-up of 7 months, 90 are evaluable.
Of the 90 pts, 34 (37%) withdrew from study during the PTL
phase; 29 for a 2nd event of G 3 or unacceptable < G 3 toxicities
Overall, 25/90 (27%) pts had G 3 diarrhea and 31/90
(34%) pts required a dose reduction of lapatinib
LAPATINIB
122 patients were accrued on this study . Adverse event data are available for
102 patients who initiated treatment (median cycles of treatment = 8 cycles)
LAPATINIB
BEVACIZUMAB
BEVACIZUMAB
Tolerability
■ A total of 29 patients (21%) have discontinued study treatment; 16
patients discontinued due to adverse events. For those patients
discontinuing treatment due to adverse events, an average of 7 cycles of
treatment were administered.
■ Seven Grade 3/4 cardiac adverse events were observed. Documented
CHF events reported in 3 patients: 1 in Arm A, and 2 in Arm B. All 3
patients discontinued study treatment at the time CHF was documented.
■ In Arm B, 1 patient died as a result of neutropenic sepsis with
enterocolitis; 1 patient died of sepsis; 1 patient experienced prolonged
hospitalization due to Typhlitis.
BEVACIZUMAB
No new or unexpected safety findings have occurred
compared with the safety profile reported for these three
chemotherapy regimens without bevacizumab.
BEVACIZUMAB
Selected common adverse events.
LVEF data for individual study
patients over time
BEVACIZUMAB
Con un total de 158 casos entre ambos estudios,
el 4-6% de las pacientes presentan disminución
significativa de la FEVi durante este tratamiento,
siendo anecdótica la aparición de toxicidad
cardíaca con expresión clínica.
BEVACIZUMAB
BEVACIZUMAB
BEVACIZUMAB
RESUMEN
TRASTUZUMAB
No parece haber un subgrupo de pacientes Her2+ de
“buen pronóstico”, por lo que siempre se debe considerar
en estos casos la opción de un tratamiento adyuvante que
incluya trastuzumab.
Hasta un 20% de pacientes puede necesitar interrumpir el
tratamiento con Trastuzumab por toxicidad cardiaca.
El esquema TC + Trastuzumab tiene una mínima toxicidad
cardiaca. Con toda seguridad esta estrategia de
tratamiento va a ver incrementado su uso en pacientes
frágiles o con riesgo cardíaco
RESUMEN
ÁCIDO ZOLEDRÓNICO EN ADYUVANCIA
Seguimos con claros datos que sugieren la utilidad de
esta estrategia de tratamiento, pero sin duda necesitamos
una confirmación en otros estudios (AZURE, SWOG 0307)
que la conviertan en un tratamiento adyuvante razonable.
LAPATINIB
A causa de la diarrea, se recomienda reducir la dosis de
Lapatinib de los 1000 mg/día a 750 mg/día cuando el
tratamiento se administra concomitante con Trastuzumab
y Paclitaxel. La toxicidad cardíaca es mínima.
RESUMEN
BEVACIZUMAB
Tres estudios demuestran la seguridad cardíaca de la
combinación del bevacizumab en esquemas con
antraciclinas y taxanos en programas de adyuvancia.
Un estudio de tratamiento primario en pacientes con
cáncer de mama operable con un esquema de tratamiento
que incluye Bevacizumab muestra una RPc en mama y
axila del 33%, superior a la habitual tasa de RPc del 1520% conseguida en grupos de pacientes similares con
esquemas basados en antraciclinas y taxanos
TRATAMIENTO PRECOZ
ESTRATEGIAS CON TERAPIAS BIOLÓGICAS