presentazione di powerpoint - aiom.it • mfs: defined as time from randomization to radiographic...
TRANSCRIPT
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
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
Hussain M et al. 2018 Genitourinary Cancers Symposium Oral Abstract Session A: Prostate Cancer
• 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
Hussain M et al. 2018 Genitourinary Cancers Symposium Oral Abstract Session A: Prostate Cancer
Median duration of therapy was 18.4 months for Enzalutamide and
11.1 months for placebo
PROSPER: Adverse Events of Special Interest
Hussain M et al. 2018 Genitourinary Cancers Symposium Oral Abstract Session A: Prostate Cancer
Baseline history of cardiovascular disease, hypertension, diabetes
mellitus, hyperlipidemia or age > 75 years
PROSPER: Progression Event by Type
Hussain M et al. 2018 Genitourinary Cancers Symposium Oral Abstract Session A: Prostate Cancer
PROSPER: Primary Endpoint MFS
Hussain M et al. 2018 Genitourinary Cancers Symposium Oral Abstract Session A: Prostate Cancer
PROSPER: Secondary Endpoint
Hussain M et al. 2018 Genitourinary Cancers Symposium Oral Abstract Session A: Prostate Cancer
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)
Hussain M et al. 2018 Genitourinary Cancers Symposium Oral Abstract Session A: Prostate Cancer
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
Small EJ et al. 2018 Genitourinary Cancers Symposium Oral Abstract Session A: Prostate Cancer
SPARTAN: Patient Characteristics
Small EJ et al. 2018 Genitourinary Cancers Symposium Oral Abstract Session A: Prostate Cancer
SPARTAN: Primary Endpoint MFS
Small EJ et al. 2018 Genitourinary Cancers Symposium Oral Abstract Session A: Prostate Cancer
72% risk reduction of distant progression or death
SPARTAN: Secondary Endpoint
Smith MR et al., NEJM 2018
SPARTAN: Adverse Events
Smith MR et al., NEJM 2018
SPARTAN: Quality of Life
Small EJ et al. 2018 Genitourinary Cancers Symposium Oral Abstract Session A: Prostate Cancer
..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.
Small EJ et al. 2018 Genitourinary Cancers Symposium Oral Abstract Session A: Prostate Cancer
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?