Pulci statistiche…

(1)

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

(2)

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

(3)

Il quesito

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

• DOC+SOC?

• ABT+SOC?

(4)

Le questioni metodologiche

1. Valutare la qualità dei risultati ottenuti 2. Descrivere il rapporto beneficio/danno

• Nei confronti diretti e indiretti a disposizione

(5)

mHSPC mCRPC nmHNPC nmCRPC

DOCETAXEL

(6)

(7)

Comparison of study PICOs

(8)

Overall survival

Failure-free survival

Vale, Lancet Oncol 2016

(9)

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

(10)

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

(11)

Primary endpoint: Overall survival

CHAARTED

Overall

(12)

High burden Low burden

CHAARTED

by tumor burden

Low precision

(13)

mHSPC mCRPC nmHNPC nmCRPC

ABIRATERONE

(14)

Comparison of study PICOs

(15)

(16)

(17)

mHNPC mCRPC nmHNPC nmCRPC

ABI vs DOCE

(18)

(19)

(20)

Slide 20

(21)

Grade 3–5 AEs in ≥2% of patients

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

(22)

QOL FACT-P: CHAARTED

(23)

LATITUDE: QOL FACT-P results

(24)

(25)

(26)

Comparison of study PICOs

(27)

Slide 32

Presented By Nicholas James at 2017 ASCO Annual Meeting

(28)

Slide 38

(29)

(30)

(31)

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

(32)

Backup Slides

(33)

MAIN INCLUSION CRITERIA

Presented By Gwenaelle Gravis at 2015 Genitourinary Cancers Symposium

(34)

Slide 13

Presented By Gwenaelle Gravis at 2015 Genitourinary Cancers Symposium

(35)

Presented By Christopher Sweeney at 2014 ASCO Annual Meeting

Risk of performance bias

(36)

STAMPEDE Trial

(37)

(38)

(39)

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)

(40)

Docetaxel: Survival

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

(41)

Slide 25

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

(42)

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

(43)

Objective

(44)

Overall study design of LATITUDE

(45)

Statistically significant 53% risk reduction of radiographic progression or death

(46)

Statistically significant 38% risk reduction of death

(47)

Summary of adverse events

(48)

Slide 1

(49)

Abiraterone comparison: patients

(50)

Inclusion criteria

(51)

Slide 30

(52)

(53)

Slide 22

(54)

Current accrual in PEACE-1

(55)

Cost of early docetaxel vs abiraterone