prostata castration resistant: oral presentations...
TRANSCRIPT
Prostata Castration Resistant: Oral Presentations
UPDATES and NEWS from the Genitourinary Cancers Symposium - Milano, 03.03.17
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
– Janssen
– Novartis
– Pfizer
Prostate Cancer: Oral Presentations
• Adjuvant androgen deprivation (ADT) versus mitoxantrone plus prednisone
(MP) plus ADT in high-risk prostate cancer (PCa) patients following radical
prostatectomy: A phase III intergroup trial (SWOG S9921) NCT00004124. Abs
#2
• Luminal and basal subtyping of prostate cancer. Abs #3
• Evaluation of the Decipher prostate cancer classifier to predict metastasis and
disease-specific mortality from genomic analysis of diagnostic prostate needle
biopsy specimens.
• Clinical significance of AR mRNA quantification from circulating tumor cells
(CTCs) in men with metastatic castration-resistant prostate cancer (mCRPC)
treated with abiraterone (Abi) or enzalutamide (Enza). Abs #132
Prostate Cancer: Oral Presentations
• Adjuvant androgen deprivation (ADT) versus mitoxantrone plus prednisone
(MP) plus ADT in high-risk prostate cancer (PCa) patients following radical
prostatectomy: A phase III intergroup trial (SWOG S9921) NCT00004124. Abs
#2
• Luminal and basal subtyping of prostate cancer. Abs #3
• Evaluation of the Decipher prostate cancer classifier to predict metastasis and
disease-specific mortality from genomic analysis of diagnostic prostate needle
biopsy specimens.
• Clinical significance of AR mRNA quantification from circulating tumor cells
(CTCs) in men with metastatic castration-resistant prostate cancer (mCRPC)
treated with abiraterone (Abi) or enzalutamide (Enza). Abs #132
Abstract #132
Silberstein J et al. J Clin Oncol 35, 2017 (suppl 6S; abstract 132) Oral Abstract Session A: Prostate Cancer
Background
• Despite androgen deprivation,
the AR continue to play a
crucial role in prostate cancer
• Liquid biopsy allows real time
investigations of the AR axis
• AR-V7 detected in CTCs may
predict outcomes to Abi/Enza
• No data has been presented on
AR-FL mRNA quantification
from CTCs
Massari F, Ciccarese C et al. Cancer Treatment Reviews 2016, 43:27–35
Azard AA et al. Clin Cancer Res 2015; 21:2315–24
AR gene aberrations in cfDNA are associated with resistance to ENZALUTAMIDE in mCRPC.
Enza: ctDNA analysis for AR amp/mut
Romanel A et al. Sci Transl Med 2015; 7:312re10
AR gene aberrations in cfDNA are associated with resistance to ABIRATERONE in mCRPC.
Abi: ctDNA analysis for AR amp/mut
Design: Prospective Biomarker Study
• 202 mCRCP patients that were about to begin therapy with Abi or
Enza
• qRT-PCR assay to interrogate CTCs for AR-FL
• Associations between baseline AR-FL status and:
• PSA response rate
• PSA progression-free survival (PSA-PFS)
• Clinical/Radiographic progression-free survival (PFS)
• Overall Survival (OS)
Silberstein J et al. J Clin Oncol 35, 2017 (suppl 6S; abstract 132) Oral Abstract Session A: Prostate Cancer
Results
• 202 patients were enrolled prior to starting Abi/Enza
• AR-FL status was considered as 3 groups:
• AR-FL Negative (Undectable): 97/202 48%
• AR-FL Positive (<Median): 52/202 26%
• AR-FL Positive (>/= Median): 53/202 26%
Silberstein J et al. J Clin Oncol 35, 2017 (suppl 6S; abstract 132) Oral Abstract Session A: Prostate Cancer
Interplay Between AR-FL and AR-V7
Silberstein J et al. J Clin Oncol 35, 2017 (suppl 6S; abstract 132) Oral Abstract Session A: Prostate Cancer
Best PSA Response
Silberstein J et al. J Clin Oncol 35, 2017 (suppl 6S; abstract 132) Oral Abstract Session A: Prostate Cancer
PSA Progression-Free Survival
Silberstein J et al. J Clin Oncol 35, 2017 (suppl 6S; abstract 132) Oral Abstract Session A: Prostate Cancer
Progression-Free Survival
Silberstein J et al. J Clin Oncol 35, 2017 (suppl 6S; abstract 132) Oral Abstract Session A: Prostate Cancer
Overall Survival
Silberstein J et al. J Clin Oncol 35, 2017 (suppl 6S; abstract 132) Oral Abstract Session A: Prostate Cancer
Summary
• CTC-based liquid biopsy allows AR-FL mRNA quantification
• Higher AR-FL levels correlate with AR-V7 posity
• Higher AR-FL correlate with inferior clinical outcomes
• AR-V7 remained independetly prognostic for all outcomes in
multivariable analyses
Silberstein J et al. J Clin Oncol 35, 2017 (suppl 6S; abstract 132) Oral Abstract Session A: Prostate Cancer
Conclusions
• AR-FL copy number is prognostic for clinical outcomes in
Abi/Enza-treated patients
• In addition to AR-V7, AR-FL quantification could serve as
another molecular biomarker of Abi/Enza sensitivity
Silberstein J et al. J Clin Oncol 35, 2017 (suppl 6S; abstract 132) Oral Abstract Session A: Prostate Cancer
Integrative Analysis of AR-ome
Silberstein J et al. J Clin Oncol 35, 2017 (suppl 6S; abstract 132) Oral Abstract Session A: Prostate Cancer
Is this study “practice changing”?
