presentación de powerpoint · etapas terapéuticas del cáncer de próstata lpc, localized or...

Dr Pablo Maroto Hospital Sant Pau

Tratamiento actual del cáncer de próstata. Situación de Enzalutamida

Dr Pablo Maroto Hospital Sant Pau

Nuevas perspectivas en el cáncer de próstata hormono-sensible metastásico

Etapas terapéuticas del cáncer de próstata

LPC, localized or locally advanced prostate cancer; mHSPC, metastatic hormone-sensitive prostate cancer; mHNPC, metastatic hormone-naive prostate cancer; mCRPC, metastatic castration-resistant

prostate cancer; M0-CRPC, non-metastatic CRPC; HR, high risk

Biochemical recurrence

mCRPC L2

mCRPC L1

Localized disease

Non-Metastatic Metastatic

M0-CRPC

mCRPC L2+

mHSPC/ mHNPC

Evolving from localized disease or newly diagnosed (de novo) mPC

Hormonosensible CPRCm

asintomático

CPRCm

Levemente sintomático

CPRCm

sintomático

CPRCm post-docetaxel

Abiraterona

Enzalutamida

Abiraterona

Enzalutamida

TDA

Docetaxel Cabacitaxel

Radio 223

Terapia soporte: denosumab, bifosfonatos

De Bono et al. N Engl J Med 2011;364:1995-2005; Ryan et al. Lancet Oncol 2015;16:152-60; Scher et al. N Engl J Med 2012;367:1187-97; Beer et al. N Engl J Med 2014;371:424-33; Parker et al. N Eng J Med 2013;369:213-23; de Bono et al.

Lancet 2010;376:1147-54; Tannock et al. N Engl J Med 2004;351:1502-12; Petrylak et al. N Engl J Med 2004;351:1513-20; Sweeney et al. N Eng J Med 2015;378:737-46; James et al. Eur J Cancer 2015;51(Suppl. 3): abstract 19LBA; Kantoff et al.

N Engl J Med 2010;363:411-22; Fizazi et al. Lancet 2011;377:813-22; Saad et al. J Natl Cancer Inst 2004;96:879-82; Sweeny C. et al. NEJM ag 2015.

No metastasico Metastásico

Hormonosensible Resistente a la castración

Asintomático Sintomático

Actualización de 2007 de la Guía de la American Society of Clinical Oncology

Bilateral orchiectomy or medical castration with luteinizing hormone–releasing hormone (LHRH) agonists are the recommended initial treatments for metastatic prostate cancer

Guías EAU 2015

Primary ADT is the standard of care. There is no level 1 evidence to choose between an LHRH analogue or antagonist, except in patients with an impending spinal cord compression. In these patients, the choice for first-line treatment is between bilateral orchidectomy and an LHRH antagonist.


asintomático

CPRCm


CPRCm

sintomático


Abiraterona

Enzalutamida

Abiraterona

Enzalutamida

TDA

TDA + Docetaxel


Radio 223








TDA + Abiraterona

Enf

Oligometastásica


asintomático

CPRCm


CPRCm

sintomático


Abiraterona

Enzalutamida

Abiraterona

Enzalutamida


Radio 223








Enf

Oligometastásica

3 o menos lesiones por PET-Colina Todas extra-craneales Niveles NO de castración de testosterona


asintomático

CPRCm


CPRCm

sintomático


Abiraterona

Enzalutamida

Abiraterona

Enzalutamida

TDA

TDA + Docetaxel


Radio 223








TDA + Abiraterona

Enf

Oligometastásica

Docetaxel: Stampede, Chaarted y Getug

Abiraterona: Stampede/Latitude

CONCLUSIONES

James N, et al. ASCO 2017. LBA5003 and Oral Abstract Session

|

|

James, N. D. et al. Addition of docetaxel, zoledronic acid, or both to first-line long-term hormone therapy in prostate cancer (STAMPEDE): Survival results from an

adaptive, multiarm, multistage, platform randomised controlled trial. Lancet 387, 1163–1177 (2016).

Relapsing after previous RP or RT with ≥1 of: • PSA ≥4ng/ml and rising with

doubling time <6m • PSA ≥20ng/ml • Node-positive • Metastatic

Newly-diagnosed Any of: • Metastatic • Node-Positive • ≥2 of: Stage T3/4

PSA≥40ng/ml Gleason 8-10

ADT = 71 m (IQR 32 to not reached) ADT + DCT = 81 m (41 to not reached) HR 0.78, 95% CI 0·66–0·93; p=0·006

CHAARTED

Sweeney, C. J. et al. Chemohormonal Therapy in Metastatic Hormone-Sensitive Prostate Cancer. N. Engl. J. Med. 2015; 373, 737–746

DEPRIVACIÓN ANDROGÉNICA

CARCINOMA DE PRÓSTATA METASTÁSICO SENSIBLE A CASTRACIÓN RECIENTE

DIAGNÓSTICO

DOCETAXEL

ALTO VOLUMEN: Visceral metastases

or ≥4 bone lesions with ≥1 beyond the vertebral

bodies and pelvis

Type of patients: Patient A: Localized PC at diagnosis that received local treatment. After a while these pts develop metastases without previous treatment with ADT for the metastatic disease* Patient B: Patient diagnosed with metastatic prostate cancer

N = 790

mFOLLOW UP = 29m

Sweeney, C. J. et al. Chemohormonal Therapy in Metastatic Hormone-Sensitive Prostate Cancer. N. Engl. J. Med. 373, 737–746 (2015).

mCSPC

Sweeney, C. J. et al. Long term efficay and …. J Clin Oncol 2018

(A) High-volume total patient population, (B) Low-volume total patient population, (C) High-volume de novo metastatic patients, (D) Low-volume de novo metastatic patients, (E) High-volume patients with prior local therapy, (F) Low-volume patients with prior local therapy

A: ADT B: ADT + DCT C: Todos los pacientes

Abdel-Rahman et al. Science Direct 2016

Docetaxel: Stampede, Chaarted y Getug

Abiraterona: Stampede/Latitude

CONCLUSIONES

LATITUDE

- Adc Próstata M1 RECIENTE DIAGNÓSTICO: SENSIBLE CASTRACIÓN

- ALTO RIESGO. 2 de: - GLEASON 8 -10 - 3 O MÁS LESIONES

ÓSEAS - METÁSTASIS

VISCERALES (MEDIBLES)

RAMDOM 1:1

ADT + PLACEBO

VS

ADT + ABIRATERONA 1000 mg + PREDNISONA

5mg

OP: - mOS - SLP RADIOGRÁFICA.

OS: - TIEMPO A :

- EVENTO ESQUELÉTICO,

- PROGRESIÓN PSA, - SIGUIENTE

TRATAMIENTO - QT - PROGRESIÓN DEL

DOLOR

Fizazi, K. et al. Abiraterone plus Prednisone in Metastatic, Castration-Sensitive Prostate Cancer. N. Engl. J. Med. NEJMoa1704174 (2017). doi:10.1056/NEJMoa1704174

FIRST INTERIM ANALYSIS Median follow-up of 30.4m

ABIRATERONA +ADT : NR ADT: 34.7m

ABIRATERONA +ADT : 33m ADT: 14.8


James, N. D. et al. Abiraterone for Prostate Cancer Not Previously Treated with Hormone Therapy. N. Engl. J. Med. NEJMoa1702900 (2017).

doi:10.1056/NEJMoa1702900

Todos los pacientes: N= 1917 Median follow-up = 40m.

James, N. D. et al. Abiraterone for Prostate Cancer Not Previously

Treated with Hormone Therapy. N. Engl. J. Med 2017

HR Todos OS: 0.63, 0.52 to 0.76; P<0.001) No mets: HR 0.75 I Mets: HR 0.61 HR SLP: 0.29; 95% CI, 0.25 to 0.34; P<0.001 No mets: 0.21 Mets: 0.31

James, N. D. et al. Addition of docetaxel, zoledronic acid, or both to first-line long-term hormone therapy in prostate cancer (STAMPEDE): Survival results from an

adaptive, multiarm, multistage, platform randomised controlled trial. Lancet 387, 1163–1177 (2016).

ENSAYO CHAARTED STAMPEDE 1 STAMPEDE 2 LATITUDE ADT VS METASTÁSICOS DOCETAXEL DOCETAXEL ABIRATERONA ABIRATERONA

100% 61% 50% 100%

ALTO RIESGO/VOLUMEN 64% X X 100%

HR OS TODOS 0.61 0.78 0.63 0.62

HR OS METASTÁSICOS 0.61 0.61 0.61 0.62

TOX 3-4 28.30% 52% 47% 63%

James et al. ESMO 2017

• La mayoría de los pacientes incluídos debutaron con metástasis. Menor evidencia para aquellos pacientes que desarrollan metástasis en el seguimiento

• Los ensayos no analizan el efecto potencial de un tratamiento precoz vs tardío

• Consideran equivalentes a Docetaxel y Abiraterona en el paciente FIT

• Decisión en función de comorbilidades, disponibilidad, sistema sanitario, etc…..

Gracias a todos

presentación de powerpoint · etapas terapéuticas del cáncer de próstata lpc, localized or...

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