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Prostata: Oral Communications Emerging strategies and controversial topics

in advanced prostate cancer

UPDATES and NEWS from the Genitourinary Cancers Symposium - Milano, 02.03.18

Francesco Massari Oncologia Medica

Azienda Ospedaliero – Universitaria di Bologna

Policlinico S. Orsola-Malpighi

Disclosures

• No pertinent C.O.I. with this presentation

• Advisory Boards/Honoraria/Consultant for:

– Astellas

– BMS

– Janssen

– Ipsen

– Pfizer

– Roche

Advanced Prostate Cancer: Oral Presentations

• PROSPER: A phase 3, randomized, double-blind, placebo (PBO)-controlled

study of enzalutamide (ENZA) in men with nonmetastatic castration-resistant

prostate cancer (M0 CRPC). Abs #3

• SPARTAN, a phase 3 double-blind, randomized study of apalutamide (APA)

versus placebo (PBO) in patients (pts) with nonmetastatic castration-resistant

prostate cancer (nmCRPC). Abs #161

• Addition of docetaxel to first-line long-term hormone therapy in prostate

cancer (STAMPEDE): Long-term survival, quality-adjusted survival, and cost-

effectiveness analysis. Abs #162

• A phase 2 study of olaparib and durvalumab in metastatic castrate-resistant

prostate cancer (mCRPC) in an unselected population. Abs #163

Abstract #3 - PROSPER

Hussain M et al. 2018 Genitourinary Cancers Symposium Oral Abstract Session A: Prostate Cancer

PROSPER: Study Design


• Primary endpoint

• MFS: defined as time from randomization to radiographic progression or

death within 112 days of treatment discontinuation

• Secondary endpoint

• Safety, Time to PSA progression, Time to use new antineoplastic therapy,

OS, PSA Response, Quality of Life

PROSPER: Baseline Patient Characteristics


Median duration of therapy was 18.4 months for Enzalutamide and

11.1 months for placebo

PROSPER: Adverse Events of Special Interest


Baseline history of cardiovascular disease, hypertension, diabetes

mellitus, hyperlipidemia or age > 75 years

PROSPER: Progression Event by Type


PROSPER: Primary Endpoint MFS


PROSPER: Secondary Endpoint


Conclusions

• In men with M0 CRPC and rapid PSA doubling time

(median 3.7 months), enzalutamide resulted in a

clinically meaningful and statistically significant 71%

reduction in the relative risk of developing M1 CRPC

• Median MFS was 36.6 months with Enzalutamide vs. 14.7

months with placebo (HR 0.29; p<0.0001)


Advanced Prostate Cancer: Oral Presentations

• PROSPER: A phase 3, randomized, double-blind, placebo (PBO)-controlled

study of enzalutamide (ENZA) in men with nonmetastatic castration-resistant

prostate cancer (M0 CRPC). Abs #3

• SPARTAN, a phase 3 double-blind, randomized study of apalutamide (APA)

versus placebo (PBO) in patients (pts) with nonmetastatic castration-resistant

prostate cancer (nmCRPC). Abs #161

• Addition of docetaxel to first-line long-term hormone therapy in prostate

cancer (STAMPEDE): Long-term survival, quality-adjusted survival, and cost-

effectiveness analysis. Abs #162

• A phase 2 study of olaparib and durvalumab in metastatic castrate-resistant

prostate cancer (mCRPC) in an unselected population. Abs #163

Abstract #161 - SPARTAN

Small EJ et al. 2018 Genitourinary Cancers Symposium Oral Abstract Session A: Prostate Cancer

SPARTAN Study

Smith MR et al., NEJM 2018

SPARTAN: Study Design

• Primary endpoint

• MFS

• Secondary endpoint

• Time to Metastasis, PFS, Time to symptomatic progression, OS, Time to

cytotoxic chemotherpy


SPARTAN: Patient Characteristics


SPARTAN: Primary Endpoint MFS


72% risk reduction of distant progression or death

SPARTAN: Secondary Endpoint


SPARTAN: Adverse Events


SPARTAN: Quality of Life


..but in an asymptomatic population, are these instruments enough sensitive to capture the psychological benefit of the decline in PSA?

Conclusions

Among men with non metastatic castration-

resistant prostate cancer, metastasis free

survival and time to symptomatic progression

were significantly longer with apalutamide

than with placebo.


What is the impetus for wanting to treat patients with M0 CRPC?

• The patient perspective

• Fear of the rising PSA and not doing anything about it

• The clinician perspective

• “..I know they have metastases anyway..”

• “Treating early might delay symptoms and might delay

use of chemotherapy”

• “Treatment earlier might prolong survival (in mHSPC

CHAARTED – STAMPEDE – LATITUDE)”

• But.. Treating asymptomatic patients carries a certain burden

of proof wherein benefit must clearly outweigh risk

What constitutes clinical benefit?

• Curing men

• Prolonging survival duration

• Improving quality of lie

• Delaying or preventing SREs has been an

approvable endpoint

SPARTAN and PROSPER How sure are we that we have made progress?

[email protected]

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