presentación de powerpoint · etapas terapéuticas del cáncer de próstata lpc, localized or...
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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.
Hormonosensible CPRCm
asintomático
CPRCm
Levemente sintomático
CPRCm
sintomático
CPRCm post-docetaxel
Abiraterona
Enzalutamida
Abiraterona
Enzalutamida
TDA
TDA + Docetaxel
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
TDA + Abiraterona
Enf
Oligometastásica
Hormonosensible CPRCm
asintomático
CPRCm
Levemente sintomático
CPRCm
sintomático
CPRCm post-docetaxel
Abiraterona
Enzalutamida
Abiraterona
Enzalutamida
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
Enf
Oligometastásica
3 o menos lesiones por PET-Colina Todas extra-craneales Niveles NO de castración de testosterona
Hormonosensible CPRCm
asintomático
CPRCm
Levemente sintomático
CPRCm
sintomático
CPRCm post-docetaxel
Abiraterona
Enzalutamida
Abiraterona
Enzalutamida
TDA
TDA + Docetaxel
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
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
Fizazi, K. et al. Abiraterone plus Prednisone in Metastatic, Castration-Sensitive Prostate Cancer. N. Engl. J. Med. NEJMoa1704174 (2017). doi:10.1056/NEJMoa1704174
Fizazi, K. et al. Abiraterone plus Prednisone in Metastatic, Castration-Sensitive Prostate Cancer. N. Engl. J. Med. NEJMoa1704174 (2017). doi:10.1056/NEJMoa1704174
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
James et al. ESMO 2017
James et al. ESMO 2017
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