Pulci Statistiche

Valter Torri IRCCS – Istituto di ricerche farmacologiche

Mario Negri - Milano

Gestione ottimale del paziente con carcinoma della prostata - Milano, 25-26.09.18

Survival remains disappointing in men presenting with M1 disease who are started on only long-term ADT, despite active treatments being available at first failure of ADT. Importantly, men with M1 disease now spend the majority of their remaining life in a state of castration-resistant relapse

Il quesito

1. Ci sono dati a favore di un cambiamento dello stato dell’arte nel trattamento del mHSPC? • DOC+SOC?

• ABT+SOC?

Le questioni metodologiche

1. Valutare la qualità dei risultati ottenuti

2. Descrivere il rapporto beneficio/danno • Nei confronti diretti e indiretti a disposizione

mHSPC mCRPC

nmHNPC nmCRPC

DOCETAXEL

Comparison of study PICOs

Overall survival

Failure-free survival

Vale, Lancet Oncol 2016

Statistical Design: History of CHAARTED<br />Intent to treat analysis, 80% power 1-sided alpha=2.5% to detect 33% improvement in median OS (with all versions)

Presented By Christopher Sweeney at 2014 ASCO Annual Meeting

CHAARTED definition of risk

High volume

visceral mets and/or ≥4 bone mets (at last 1 beyond pelvis and spine)

Presented By Michael Morris at 2014 ASCO Annual Meeting

Primary endpoint: Overall survival

CHAARTED Overall

High burden Low burden

CHAARTED by tumor burden

Low precision

mHSPC mCRPC

nmHNPC nmCRPC

ABIRATERONE

Comparison of study PICOs

mHNPC mCRPC

nmHNPC nmCRPC

ABI vs DOCE

Slide 20

Grade 3–5 AEs in ≥2% of patients

Presented By Nicholas Van As at 2018 Genitourinary Cancers Symposium: Translating Evidence to Multidisciplinary Care

QOL FACT-P: CHAARTED

Presented By Nicholas Van As at 2018 Genitourinary Cancers Symposium: Translating Evidence to Multidisciplinary Care

LATITUDE: QOL FACT-P results

Presented By Nicholas Van As at 2018 Genitourinary Cancers Symposium: Translating Evidence to Multidisciplinary Care

Comparison of study PICOs

Slide 32

Presented By Nicholas James at 2017 ASCO Annual Meeting

Slide 38

Presented By Nicholas James at 2017 ASCO Annual Meeting

Network meta-analyses of aggregate data suggest “abiraterone” better

Presented By Nicholas Van As at 2018 Genitourinary Cancers Symposium: Translating Evidence to Multidisciplinary Care

Backup Slides

MAIN INCLUSION CRITERIA

Presented By Gwenaelle Gravis at 2015 Genitourinary Cancers Symposium

Slide 13

Presented By Gwenaelle Gravis at 2015 Genitourinary Cancers Symposium

Presented By Christopher Sweeney at 2014 ASCO Annual Meeting

Risk of performance bias

STAMPEDE Trial

Presented By Nicholas James at 2017 ASCO Annual Meeting

Presented By Nicholas James at 2017 ASCO Annual Meeting

Presented By Nicholas James at 2017 ASCO Annual Meeting

HR (95% CI) SOC+ZA vs. SOC: 0.94 (0.79-1.11) SOC+DOC vs. SOC: 0.78 (0.66-0.93) SOC+ZA+DOC vs. SOC: 0.82 (0.69-0.97)

Docetaxel: Survival

Presented By Nicholas James at 2018 Genitourinary Cancers Symposium: Translating Evidence to Multidisciplinary Care

Slide 25

Presented By Nicholas James at 2018 Genitourinary Cancers Symposium: Translating Evidence to Multidisciplinary Care

LATITUDE: A phase 3, double-blind, randomized trial of androgen deprivation therapy with abiraterone acetate plus prednisone or placebos <br />in newly diagnosed high-risk metastatic hormone-naïve prostate cancer patients

Presented By Karim Fizazi at 2017 ASCO Annual Meeting

Objective

Presented By Karim Fizazi at 2017 ASCO Annual Meeting

Overall study design of LATITUDE

Presented By Karim Fizazi at 2017 ASCO Annual Meeting

Statistically significant 53% risk reduction of radiographic progression or death

Presented By Karim Fizazi at 2017 ASCO Annual Meeting

Statistically significant 38% risk reduction of death

Presented By Karim Fizazi at 2017 ASCO Annual Meeting

Summary of adverse events

Presented By Karim Fizazi at 2017 ASCO Annual Meeting

Slide 1

Presented By Nicholas James at 2017 ASCO Annual Meeting

Abiraterone comparison: patients

Presented By Nicholas James at 2017 ASCO Annual Meeting

Inclusion criteria

Presented By Nicholas James at 2017 ASCO Annual Meeting

Slide 30

Presented By Nicholas James at 2017 ASCO Annual Meeting

Slide 22

Presented By Nicholas Van As at 2018 Genitourinary Cancers Symposium: Translating Evidence to Multidisciplinary Care

Current accrual in PEACE-1

Presented By Nicholas Van As at 2018 Genitourinary Cancers Symposium: Translating Evidence to Multidisciplinary Care

Cost of early docetaxel vs abiraterone

Presented By Nicholas Van As at 2018 Genitourinary Cancers Symposium: Translating Evidence to Multidisciplinary Care