Sergio Bracarda MD, Head, Department of Oncology Azienda USL Toscana Sud-Est Istituto Toscano Tumori (ITT) Ospedale San Donato Arezzo, Italy
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1 Sergio Bracarda MD, Head, Department of Oncology Azienda USL Toscana Sud-Est Istituto Toscano Tumori (ITT) Ospedale San Donato Arezzo, Italy Milano, 3 marzo 2017
2 Prostata: Castration resistant HIGHLIGHTS Outline Molecular Drivers in mcrpc Genomic alterations Genomic evolution in PC Significantly mutated genes in mcrpc Cinzia Ortega Oncologia ASLCN2 Liquid Biopsies AR indifferent disease
3 MOLECULAR DRIVERS IN mcrpc Genomic alterations Systematic and multi-institutional study of mcrpc tumors obtained from living affected individuals to determine the landscape of somatic genomic alterations genomic differences between primary prostate cancer and mcrpc Robinson et al, Cell 2015
4 Genomic heterogeneity in prostate cancer Presented By Eliezer Van Allen at 2017 Genitourinary Cancers Symposium
5 The most frequently aberrant genes in mcrpc included AR (62.7%), ETS family (56.7%), TP53 (53.3%) and PTEN (40.7%) Presented By Joshua Lang at 2017 Genitourinary Cancers Symposium (modified) Robinson et al, Cell 2015
6 Aberrations in the AR pathway Key genes altered Point mutations Presented By Joshua Lang at 2017 Genitourinary Cancers Symposium (modified) Robinson et al, Cell 2015
7 Scher et al. JAMA Oncol Jun 4.
8 Slide 11 Presented By Gerhardt Attard at 2017 Genitourinary Cancers Symposium
9 No change in AR copy <br />number on abiraterone Presented By Gerhardt Attard at 2017 Genitourinary Cancers Symposium
10 Plasma AR is associated with worse outcome in PREMIERE trial Presented By Gerhardt Attard at 2017 Genitourinary Cancers Symposium
11 Robinson et al Cell 2015 Presented By Joshua Lang at 2017 Genitourinary Cancers Symposium
12 200 mg Ipatasertib 400 mg Ipatasertib ALLAN MARTIN STUDY: CO-PRIMARY ENDPOINT: RPFS WITH IPATASERTIB OR PLACEBO + ABIRATERONE BY ICR IHC PTEN loss PTEN non-loss HR, a 0.39 ( ) 400 mg Ipat + Abi Median 11.5 mo Pbo + Abi Median 4.6 mo HR, a 0.84 ( ) 400 mg Ipat + Abi Median 7.5 mo Pbo + Abi Median 5.6 mo HR, a 0.46 ( ) 200 mg Ipat + Abi Median 11.1 mo 200 mg Ipat + Abi Median 4.6 mo HR, a 1.13 ( ) Pbo + Abi Median 4.6 mo Pbo + Abi Median 5.6 mo a Unstratified HR; 90% CI. Courtesy de Bono et al, Ipatasertib, ESMO 2016
13 DNA Repair & Metastatic PCa Presented By James Catto at 2017 Genitourinary Cancers Symposium
14 DNA Repair & Metastatic PCa Presented By James Catto at 2017 Genitourinary Cancers Symposium
15 Slide 11 Will the practice change? Presented By Joshua Armenia at 2017 Genitourinary Cancers Symposium
16 Presented By Ana Aparicio at 2017 Genitourinary Cancers Symposium
17 Cabazitaxel +/- Carboplatin in mcrpc Will the practice change? Presented By Ana Aparicio at 2017 Genitourinary Cancers Symposium
18 Prostata Castration Resistant: Oral Presentations Francesco Massari Oncologia Medica Azienda Ospedaliero Universitaria di Bologna Policlinico S. Orsola-Malpighi UPDATES and NEWS from the Genitourinary Cancers Symposium - Milano,
19 Abstract #132 Silberstein J et al. J Clin Oncol 35, 2017 (suppl 6S; abstract 132) Oral Abstract Session A: Prostate Cancer
20 Enza: ctdna analysis for AR amp/mut AR gene aberrations in cfdna are associated with resistance to ENZALUTAMIDE in mcrpc. Azard AA et al. Clin Cancer Res 2015; 21:
21 Abi: ctdna analysis for AR amp/mut AR gene aberrations in cfdna are associated with resistance to ABIRATERONE in mcrpc. Romanel A et al. Sci Transl Med 2015; 7:312re10
22 Results Overall Survival 202 pts 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
23 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 Will the practice change? Silberstein J et al. J Clin Oncol 35, 2017 (suppl 6S; abstract 132) Oral Abstract Session A: Prostate Cancer
24 Revisione Posters Prostata Castration Resistant: CTC: Fattori prognostici/predittivi, Sequenze Immunoterapia, Trattamenti combinati Prostata: Castration Resistant Revisione Posters 1) CTC: Fattori prognostici/predittivi 2) Sequenze 3) Immunoterapia 4) Trattamenti combinati
25 1) CTC and Prognostic/Predictive Markers: - CTC Count - NGS - CgA
26 2) mcrpc, Stage IV Treatment Options: The Sequencing Dilemma : New HT Drug-1 followed by new HT Drug-2?. the inverse Sequencing? or Chemotherapy? (. this is the problem..)
27 Metastatic disease: STRIVE RCT Will the practice change? Presented By James Catto at 2017 Genitourinary Cancers Symposium
28 3) I-O Phase 1b Trial of Anti-PD-1<br />17 Prostate Cancer Patients. Will the practice change? Presented By Charles Drake at 2017 Genitourinary Cancers Symposium
29 4) Combo Cryo + PD-1 Blockade Will the practice change? Presented By Charles Drake at 2017 Genitourinary Cancers Symposium
30 CONCLUSIONS Will the Practice Change for CRPC in 2017? surely not because of what presented at 2017 GUSY!!!
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