La innovación como garantía de calidad asistencial:

Cáncer de próstata Javier Puente, MD, PhD Hospital Universitario Clinico San Carlos Medical Oncology Department Complutense University Associate Professor of Medicine

Innovación en Cáncer de Próstata

Introduction

- Since the approval of docetaxel we have learned much about the biology of prostate cancer - Multiple new drugs have demostrated safety and efficacy leading to aproval

Treament algorithm

Where We Are Now: Positive Phase 3 Trials in Met CRPC

Innovación en Cáncer de Próstata Nuevos datos en CPRCM1 con Enzalutamida y Abiraterona

Papel de docetaxel en CPHSM1

Papel de docetaxel en CP localizado de alto riesgo

Nuevas entidades AP en el cáncer de próstata

Innovación en Cáncer de Próstata Nuevos datos en CPRCM1 con Enzalutamida y Abiraterona

Papel de docetaxel en CPHSM1

Papel de docetaxel en CP localizado de alto riesgo

Nuevas entidades AP en el cáncer de próstata

CPRCm

Unfit - ECOG ≥2 - Mala reserva medular: (pl < 100000, n: < 1000) - Neuropatía G2 - Comórbido, añoso

Radium-223 ¿Abi/Enza?

Fit

Paciente asintomático o mínimamente sintomático ECOG 0-1

Tto. Hormonal

Paciente con metástasis hepáticas y/o viscerales

Quimioterapia

Pacientes sintomáticos o con deterioro general por el tumor

Abiraterone in Metastatic prostate cancer without previous chemotherapy R A N D O M I Z E D

Patient Population Progressive mCRPC without prior chemotherapy; Asymptomatic or mildly symptomatic

Co-primary end points: Abiraterone 1000 mg daily + Prednisone 5 mg BID (actual n = 546)

aStratification by

• OS

Secondary end points: • Time to opiate use • Time to initiation of chemotherapy • Time to ECOG PS deterioration • Time to PSA progression

Placebo daily + Prednisone 5 mg BID (actual n = 542)

1:1a

• rPFS (central review)

ECOG PS 0 vs 1.

IA3 Unblinding FPI 2008

2009

LPI 2010

IA1

IA2 2011

FA 2012

2013

2014

OS with Abiraterone in mCRPC: median follow-up of 49.2 months

Treatment effect more pronounced when adjusting for 44% of prednisone patients who received subsequent abiraterone (HR = 0.74)

Third interim analysis data of rPFS

Abiraterone in mCRPC (COU-302): secondary endpoints

Abiraterone in mCRPC (COU-302): safety

PREVAIL: A phase 3 trial of enzalutamide after progression on ADT in men with mCRPC Patient population: •1717 men with progressive mCRPC •Asymptomatic/ mildly symptomatic •Chemotherapy-naïve •Steroids allowed but not required

R A N D O M I Z E D 1:1

Enzalutamide 160 mg/day (capsules) n=872

Co-primary endpoints: • OS

• rPFS

Placebo n=845

Enzalutamide reduced risk of death by 29% Enzalutamide Reduced Risk of Death by 29%

Enzalutamide prolonged radiographic PFS Enzalutamide Prolonged Radiographic
Progression-Free Survival

Secondary endpoints with Enzalutamide in the PREVAIL trial

Most common Adverse Events


Most Common Adverse Events*


CPRCm

Unfit - ECOG ≥2 - Mala reserva medular: (pl < 100000, n: < 1000) - Neuropatía G2 - Comórbido, añoso

Radium-223 ¿Abi/Enza?

Fit

Paciente asintomático o mínimamente sintomático ECOG 0-1

ABiRATERONA VS ENZALUTAMIDA

Paciente con metástasis hepáticas y/o viscerales

Quimioterapia

Pacientes sintomáticos o con deterioro general por el tumor

Outcomes are evaluated by changes in disease manifestations PRESENT or which MAY OCCUR in the future

Scher et al. Urology 2000

CPRCM0

CPRCm

Unfit

Fit

- ECOG ≥2 - Mala reserva medular: (pl < 100000, n: < 1000) - Neuropatía G2 - Comórbido, añoso

Paciente asintomático o mínimamente sintomático ECOG 0-1

PSADT corto Gleason 8-10 LDH ↑ FA ↑ Resp. HT corto

Radium-223 ¿Abi/Enza?

ABiRATERONA VS ENZALUTAMIDA

Paciente con metástasis hepáticas y/o viscerales

ECOG 0 Oligometast Nodular pulmonar?

Quimioterapia

Pacientes sintomáticos o con deterioro general por el tumor

Where are we going from here?

Where are we going from here?

Crawford ED, et al.ASCO 2014

CPRCM0

CPRCm

Unfit

Fit

- ECOG ≥2 - Mala reserva medular: (pl < 100000, n: < 1000) - Neuropatía G2 - Comórbido, añoso

Paciente asintomático o mínimamente sintomático ECOG 0-1

PSADT corto Gleason 8-10 LDH ↑ FA ↑ Resp. HT corto

Radium-223 ¿Abi/Enza?

CPHSm1

ABiRATERONA VS ENZALUTAMIDA

Paciente con metástasis hepáticas y/o viscerales

ECOG 0 Oligometast Nodular pulmonar?

Quimioterapia

Pacientes sintomáticos o con deterioro general por el tumor

Innovación en Cáncer de Próstata Nuevos datos en CPRCM1 con Enzalutamida y Abiraterona

Papel de docetaxel en CPHSM1

Papel de docetaxel en CP localizado de alto riesgo

Nuevas entidades AP en el cáncer de próstata

The natural history of metastatic, hormone-naïve prostate cancer Abiraterone, Enzalutamide, Docetaxel, Cabazitaxel, Radium-223, Denosumab

ADT M1 HSPC

M1 HSPC UNDER CONTROL

CRPC

Time (Median 4-5 years)

THE END

The natural history of metastatic, hormone-naïve prostate cancer Hypothesis of CHAARTED and GETUG 15 phase III trials: - Early docetaxel will postpone progression to CRPC - Early docetaxel will postpone death

M1 HSPC

M1 HSPC UNDER CONTROL

Time to progression Time to death

CRPC

THE END

M1 HSMPC: 2 scenarios

Docetaxel in HSPC: CLINICAL PFS IS IMPROVED

Docetaxel in HSPC: Overall Survival

Patient characteristics CHAARTED ADT + Doc (N=397)

ADT alone (N=393)

N

%

N

%

Low

134

33.8%

142

36.1%

High

263

66.2%

251

63.9%

4-6

21

5.9%

21

6.1%

7

96

26.9%

82

23.9%

8-10

240

67.2%

240

70.0%

Volume of Mets

Gleason Score

Unknown

40 PSA (ng/mL) at time of ADT start

50

Median

56.0

50.5

Range

0.4-8540.1

0.1-8056.0

OS by extend of metastatic disease at start of ADT

Baseline Characteristics in GETUG-15

Slide 12

Presented By Gwenaelle Gravis at 2015 ASCO GU

Key differences GETUG – E3805 •Case-Mix/Patient Characteristics • Lower burden of disease • Overall patients in GETUG15 on ADT alone had longer OS than E3805

•Access to more lines of therapy once CRPC • More non-LHRH therapy in E3805

•Sample size • GETUG15 half the sample size; less power

•More non-PrCa and Rx related deaths: • Dilute the cancer control benefits (longer time to CRPC ADT+doc in GETUG15) • Greater dilution of potential OS benefit from decrease prostate cancer deaths if increase competing risks from other deaths if longer OS on ADT alone

Slide 1

Presented By Nicholas James at 2015 ASCO Annual Meeting

Inclusion criteria

Presented By Nicholas James at 2015 ASCO Annual Meeting

Outcome measures

Presented By Nicholas James at 2015 ASCO Annual Meeting

Docetaxel & ZA comparisons: patients

Presented By Nicholas James at 2015 ASCO Annual Meeting

Accrual

Presented By Nicholas James at 2015 ASCO Annual Meeting

Zoledronic acid: Failure-free survival

Presented By Nicholas James at 2015 ASCO Annual Meeting

Zoledronic acid: Survival

Presented By Nicholas James at 2015 ASCO Annual Meeting

Docetaxel: Failure-free survival

Presented By Nicholas James at 2015 ASCO Annual Meeting

Docetaxel: Survival

Presented By Nicholas James at 2015 ASCO Annual Meeting

Zoledronic acid + docetaxel: Failure-free survival

Presented By Nicholas James at 2015 ASCO Annual Meeting

Zoledronic acid + docetaxel: Survival

Presented By Nicholas James at 2015 ASCO Annual Meeting

Docetaxel: Survival – M1 Patients

Presented By Nicholas James at 2015 ASCO Annual Meeting

CPRCM0

CPRCm

Unfit

CPLocal

Fit

- ECOG ≥2 - Mala reserva medular: (pl < 100000, n: < 1000) - Neuropatía G2 - Comórbido, añoso

Paciente asintomático o mínimamente sintomático ECOG 0-1

PSADT corto Gleason 8-10 LDH ↑ FA ↑ Resp. HT corto

Radium-223 ¿Abi/Enza?

CPHSm1

ABiRATERONA VS ENZALUTAMIDA

Paciente con metástasis hepáticas y/o viscerales

ECOG 0 Oligometast Nodular pulmonar?

Quimioterapia

Pacientes sintomáticos o con deterioro general por el tumor

Innovación en Cáncer de Próstata Nuevos datos en CPRCM1 con Enzalutamida y Abiraterona

Papel de docetaxel en CPHSM1

Papel de docetaxel en CP localizado de alto riesgo

Nuevas entidades AP en el cáncer de próstata

Docetaxel for localized, high-risk prostate cancer (RTOG 0521) Slide 3

Presented By Howard Sandler at 2015 ASCO Annual Meeting

Docetaxel for localized, high-risk prostate cancer (RTOG 0521) Slide 4

Presented By Howard Sandler at 2015 ASCO Annual Meeting

Docetaxel for localized, high-risk prostate cancer (RTOG 0521): DFS Slide 14

Presented By Howard Sandler at 2015 ASCO Annual Meeting

Docetaxel for localized, high-risk prostate cancer (RTOG 0521): OS

Slide 12

Presented By Howard Sandler at 2015 ASCO Annual Meeting

OVERAL SURVIVAL

Where are we going from here? • Additional uses for approved drugs • Additional (generally earlier) settings • Combinations

• New versions of similar drugs • Treatment optimization • Mechanisms of resistance • Sequencing, combinations, biomarkers • New targets/drugs • New disease classifications • Precision medicine

Innovación en Cáncer de Próstata Nuevos datos en CPRCM1 con Enzalutamida y Abiraterona

Papel de docetaxel en CPHSM1

Papel de docetaxel en CP localizado de alto riesgo

Nuevas entidades AP en el cáncer de próstata

Dream Team Biopsy Trial

Dream Team Biopsy Trial

Presented By Eric Small at 2015 ASCO Annual Meeting

Dream Team Biopsy Trial: histology of 124 evaluable biospies

Histology of 124 Evaluable Biopsies
74 % were “pure” with a single histologic subtype (**isolated by LCM)
Remainder (26%) were comprised of mixed populations

Presented By Eric Small at 2015 ASCO Annual Meeting

Dream Team Biopsy Trial: IAC

Slide 15

Presented By Eric Small at 2015 ASCO Annual Meeting

Dream Team Biopsy Trial: histology of 124 evaluable biospies

IAC and SCNC are equally distributed across all tissue types

Presented By Eric Small at 2015 ASCO Annual Meeting

Dream Team Biopsy Trial: histology of 124 evaluable biospies

Overall survival as function of biopsy pathology
Grouping IAC and SCNC

Presented By Eric Small at 2015 ASCO Annual Meeting

THANK YOU Javier Puente, MD, PhD Hospital Universitario Clinico San Carlos Medical Oncology Department Complutense University Associate Professor of Medicine