Nuevas perspectivas en el cáncer de próstata hormono-sensible metastásico Tratamiento actual del cáncer de próstata. Situación de Enzalutamida Dr Pablo Maroto Hospital Sant Pau Dr Pablo Maroto Hospital Sant Pau
Etapas terapéuticas del cáncer de próstata Non-Metastatic Evolving from localized disease or newly diagnosed (de novo) mpc mhspc/ mhnpc Metastatic Localized disease Biochemical recurrence mcrpc L1 mcrpc L2 mcrpc L2+ M0-CRPC 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
Hormonosensible CPRCm asintomático CPRCm Levemente sintomático CPRCm sintomático CPRCm postdocetaxel TDA Abiraterona Abiraterona Enzalutamida Enzalutamida Actualización de 2007 de la Guía de la American Society of Clinical Oncology Docetaxel Cabacitaxel Bilateral orchiectomy or medical castration with luteinizing hormone releasing hormone (LHRH) agonists are the recommended initial treatments for metastatic prostate cancer Radio 223 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. Terapia soporte: denosumab, bifosfonatos Hormonosensible No metastasico Asintomático Resistente a la castración Metastásico Sintomático 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.
Hormonosensible CPRCm asintomático CPRCm Levemente sintomático CPRCm sintomático CPRCm postdocetaxel TDA Abiraterona Abiraterona TDA + Docetaxel Enzalutamida Enzalutamida TDA + Abiraterona Docetaxel Cabacitaxel Enf Oligometastásica Radio 223 Terapia soporte: denosumab, bifosfonatos Hormonosensible No metastasico Resistente a la castración Metastásico Asintomático Sintomático 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.
Hormonosensible CPRCm asintomático CPRCm Levemente sintomático CPRCm sintomático CPRCm postdocetaxel Abiraterona Abiraterona Enzalutamida Enzalutamida Docetaxel Cabacitaxel Enf Oligometastásica Radio 223 Terapia soporte: denosumab, bifosfonatos Hormonosensible No metastasico Resistente a la castración Metastásico Asintomático Sintomático 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.
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 postdocetaxel TDA Abiraterona Abiraterona TDA + Docetaxel Enzalutamida Enzalutamida TDA + Abiraterona Docetaxel Cabacitaxel Enf Oligometastásica Radio 223 Terapia soporte: denosumab, bifosfonatos Hormonosensible No metastasico Resistente a la castración Metastásico Asintomático Sintomático 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.
Docetaxel: Stampede, Chaarted y Getug Abiraterona: Stampede/Latitude CONCLUSIONES
Newly-diagnosed Any of: Metastatic Node-Positive 2 of: Stage T3/4 PSA 40ng/ml Gleason 8-10 Relapsing after previous RP or RT with 1 of: PSA 4ng/ml and rising with doubling time <6m PSA 20ng/ml Node-positive Metastatic James, N. D. et al. Addition James N, of et docetaxel, al. ASCO 2017. zoledronic LBA5003 acid, and or Oral both Abstract to first-line Session long-term hormone therapy in prostate cancer (STAMPEDE): Survival results from an adaptive, multiarm, multistage, platform randomised controlled trial. Lancet 387, 1163 1177 (2016).
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
ALTO VOLUMEN: Visceral metastases or 4 bone lesions with 1 beyond the vertebral bodies and pelvis DEPRIVACIÓN ANDROGÉNICA CHAARTED DOCETAXEL 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 CARCINOMA DE PRÓSTATA METASTÁSICO SENSIBLE A CASTRACIÓN RECIENTE DIAGNÓSTICO Sweeney, C. J. et al. Chemohormonal Therapy in Metastatic Hormone-Sensitive Prostate Cancer. N. Engl. J. Med. 2015; 373, 737 746
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 (A) High-volume total patient population, (B) Lowvolume 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 Sweeney, C. J. et al. Long term efficay and. J Clin Oncol 2018
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
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 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
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