Coordinación científica: Dr. Fernando Rivera Hospital Universitario Marqués de Valdecilla,

Santander

Organizado por: Fundación para el progreso

de la oncología en Cantabria

Novedades en el manejo del paciente con CPRC M0

y su potencial aplicación en la clínica

Dr. Juan Fco Rodríguez Moreno Centro Integral Oncológico Clara Campal. Madrid

M0 Prostate Cancer: A trending topic in GU oncology

www.thelancet.com/oncology Vol 19 April 2018

N Engl J Med 378;26 nejm.org June 28, 2018

M0 Prostate Cancer: Definition and Review of the problem

1.1 million Prostate Cancers diagnosed annually in the world

Most of them in early stages with curative options of treatment

Relapses after local radical treatments (Surgery or Radiotherapy) could be only a Biochemical

Recurrence:

RISING SERUM PSA WITHOUT LOCOREGIONAL RECURRENCE OR DISTANT METASTASES

Androgen Deprivation Therapy, YES…..BUT

When to initiate ADT-Based Therapy?

Monotherapy?

Continuous versus intermittent androgen deprivation

Van den Bergh RC et al. Eur Urol. 2016:69(5):802

Crook et al. N Engl J Med 2012:367(10):895

M0 Castration-Resistant Prostate Cancer: Definition and Review of the problem

US incidence of nmCRPC is approximately 50.000 to 60.000 cases per year.

Men with nmCRPC are not at risk for recurrence, are sick people in which metastatic disease will be

appear if don´t die for another cause.

In many cases of nmCRPC the median bone metastasis-free survival ranges from 25 to 30 months.

But, some prognostics features could select a high risk population for develop distant metastasis; like

PSA level, PSA DT, Gleason Score, etc.

Watchful waiting ??

Denosumab?

Atrasentan, Zibotentan, …

Clinical Trials: SPARTAN and PROSPER Smith MR et al. J Clin Oncol 2005; 23:2918-25

Smith MR et al. Cancer 2011. 117:2077-85

Smith MR et al. J Clin Oncol 2013:31:3800-6

Smith MR et al. N Engl J Med Feb 2018;378:1408-18

M Hussain et al. N Engl J Med Jun 2018;378:2465-74

Smith MR et al. N Engl J Med Feb 2018;378:1408-18

M Hussain et al. N Engl J Med Jun 2018;378:2465-74

*

SPARTAN & PROSPER Trials: Common aspects

Big (1207 & 2874 pts) prospective Phase 3, double-blind, placebo-controlled, randomized (2:1) trials

M0 = Non-Metastatic Disease assessed by CT scan and Bone Scan

* N1 patients (pelvic lymph nodes less 2cm) were allowed in SPARTAN Trial

PSA DT ≤ 10 Months

Stratified according to:

* PSA DT > 6m vs ≤ 6m

* Use of bone-sparing agents

* and N0 vs N1 in the SPARTAN Trial

Primary end-point: Metastasis-free Survival

JA Beaver et al. N Engl J Med 378;26 nejm.org June 28, 2018

SPARTAN & PROSPER Trials: Common aspects

Big (1207 & 2874 pts) prospective Phase 3, double-blind, placebo-controlled, randomized (2:1) trials

M0 = Non-Metastatic Disease assessed by CT scan and Bone Scan

* N1 patients (pelvic lymph nodes less 2cm) were allowed in SPARTAN Trial

PSA DT ≤ 10 Months

Stratified according to:

* PSA DT > 6m vs ≤ 6m

* Use of bone-sparing agents

* and N0 vs N1 in the SPARTAN Trial

Primary end-point: Metastasis-free Survival

JA Beaver et al. N Engl J Med 378;26 nejm.org June 28, 2018

Xie M, et al. J Clin Oncol, 2017

SPARTAN Trial: Efficacy

SPARTAN Trial:

Efficacy

SPARTAN Trial:

Efficacy

PROSPER Trial: Efficacy

PROSPER

Efficacy

PROSPER

Efficacy

Enzalutamide Associated with Stable to Improved QOL by FACT-P

Presented By Alicia Morgans at 2018 ASCO Annual Meeting

E.J Small. Poster. AUA Annual Meeting 2018

TOXICITY

Fracture 17 vs 8%

TOXICITY

Death principally related with Cardiovascular Events. More frequent in:

* Patients with personal history of cardiovascular disease

* Hypertension

* Diabetes Mellitus

* Hyperlipidemia

* 75 years of age or older

So, in the clinic… SELECT AND MONITOR patients carefully

Really M0?? Try PET-Colina or PET-PSMA

So, in the clinic… SELECT AND MONITOR patients carefully

Really M0?? Try PET-Colina or PET-PSMA

So, in the clinic… SELECT AND MONITOR patients carefully

Really M0??

Agresive disease?? PSA DT <10m?? PSA DT <6m?? PSA level?? Gleason Score??

J Clin Oncol 36,2018(suppl; abst 5034

So, in the clinic… SELECT AND MONITOR patients carefully

Really M0??

Agresive disease??

Patient fit for second generation AA??

* Cardiovascular comorbilities

* Neurological comorbilities

* Downton Scale <3

* Age??

So, in the clinic… SELECT AND MONITOR patients carefully

Really M0??

Agresive disease??

Patient fit for second generation AA??

Close Monitoring, specially BONE HEALTH

* Increase the use of bone-sparing agents

So, in the clinic… SELECT AND MONITOR patients carefully

Really M0??

Agresive disease??

Patient fit for second generation AA??

Close Monitoring, specially BONE HEALTH

Regulatory issues

Coordinación científica: Dr. Fernando Rivera Hospital Universitario Marqués de Valdecilla,

Santander

Organizado por: Fundación para el progreso

de la oncología en Cantabria

Thank you for your attention!

jfrodriguez@hmhospitales.com