Sergio Bracarda MD, Medical Oncology, Dept. Of Oncology Az. Ospedaliera S. Maria, Terni; Italy. Milano, 2 marzo 2019

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1 Sergio Bracarda MD, Medical Oncology, Dept. Of Oncology Az. Ospedaliera S. Maria, Terni; Italy Milano, 2 marzo 2019

2 My Disclosure Adv. Board Member for: Pfizer, BMS, Novartis, MSD, Roche, Genentech, Astellas, Janssen, Eusa Pharma, Ipsen, Exelixis. Travel Accomodation with: Pfizer, BMS, Roche, Astellas, Jannsen, Ipsen. Bayer Reasonable Honoraria (Talks) from: Pfizer, Roche, Astellas,Novartis, BMS, Janssen

3 Highlights New treatment strategies for CRPC M0 - New hormonal agents - Biomarkers - Immunotherapy Carcinoma della Prostata: Malattia localizzata e localmente avanzata Salvatore Siena Ospedale Niguarda RiccardoCa Ricotta Granda, Milano Niguarda Cancer Center Ospedale Niguarda, Milano Abstracts Imaging Presented By Daniel Hamstra at 2019 Genitourinary Cancers Symposium

4 Presented By Ian Davis at 2019 Genito- Urinary Cancers Symposium M0 CRPC: a condition needing treatment?

5 Presented By Karim Fizazi at 2019 GU Cancers Symposium

6 Baseline patient characteristics ARAMIS endpoints Presented By Karim Fizazi at 2019 Genitourinary Cancers Symposium Presented By Karim Fizazi at 2019 Genitourinary Cancers Symposium

7 TEAEs of interest Presented By Karim Fizazi at 2019 Genitourinary Cancers Symposium

8 Presented By Eric Small at 2019 Genitourinary Cancers Symposium SPARTAN Randomized, Phase 3, Placebo-Controlled Trial<br />

9 Presented By Eric Small at 2019 Genitourinary Cancers Symposium Slide 7

10 M0-CRPC Disease: a Twin Trial Comparison

11 Spartan Prosper

12 MO (High-Risk non-metastatic CRPC) Primary endpoint (for both the Trials):MFS (met.-free surv.) Aramis Median Advantage in MFS: about mts Hussain M, et al. N Engl J Med. 2018; Smith MR, et al. N Engl J Med. 2018

13 MO (High-Risk non-metastatic CRPC) Primary endpoint (for both the Trials):MFS (met.-free surv.) Median Advantage in MFS: about 24 mts But, which advantages in OS? Was the right Population selected? Slide 13 Overall Survival: First Interim Analysis Presented By Eric Small at 2018 Genitourinary Cancers Symposium: Translating Evidence to Multidisciplinar Presented By Maha Hussain at 2018 Genitourinary Cancers Symposium: Translating Evidence to Multidisciplinary Care Hussain M, et al. N Engl J Med. 2018; Smith MR, et al. N Engl J Med. 2018

14 Basal-Luminal Status is Associated <br />with Response to Apalutamide Decipher Presented By Felix Feng at 2019 Genitourinary Cancers Symposium

15 Presented By Felix Feng at 2019 Genitourinary Cancers Symposium Decipher Gene signature assay

16 Negative Predictive Value Presented By Scott Williams at 2019 Genitourinary Cancers Symposium Freedom from progression (FFP) = time during which the patient was free from cancer progression The Primary EndPoint was to determine whether FCH was more effective as a FLI approach in changing management Secondary EndPoints included incremental utility of SLI and negative predictive value (NPV) based on PFS

17 A study of intense neoadjuvant testosterone lowering therapy with goserelin and enzalutamide in high-risk prostate cancer (PC) with multiparametric MRI (mpmri) Karzai F, et al. Abstract # 63 Molecular and imaging correlates of exceptional pathologic response to neoadjuvant ADT plus enzalutamide Sowalsky AG, et al. Abstr#61 FFPE sections of tumor analyzed using whole exome sequencing RCB Results: - Gleason score at baseline did not differentiate responding and nonresponding pts - ERG expression and the presence of intraductal carcinoma architecture at baseline were negatively associated with response (residual tumor burden < 0.05 cc) - Focal PTEN loss was observed in all nonresponders at baseline. - Responding tumor foci were enriched for deletion of chromosome 6q - mpmri changes, especially in DCE-MRI, distinguish between responders and nonresponders Preoperative trial of neoadjuvant abiraterone plus or minus cabazitaxel: Early results. Herrera-Caceres JO, et al. Abstract #98 Phase II randomized trial in 76 pts with High-risk PCa - Arm A (AA/P + LHRH + Cabazitaxel with peg-filgrastim x 6 cycles) vs Arm B (AA/P + LHRH) for 6 months prior to RP - The primary objective is to compare the pathological CR between the treatment arms. - Outcomes and safety data for the first 13 participants (10 completed procedures and underwent RP) Conclusions: Response to treatment correlates with distinctive pathologic, molecular, and imaging features that can be observed prior to treatment. Selection of patients based on these parameters may improve overall responses to treatment in subsequent clinical trials A randomized phase Ib/II study of nivolumab with or without BMS in combination with a short course of ADT in men with castration-sensitive prostate cancer (MAGIC-8) Allos M, et al. Abstr #TPS329 Biochemically-recurrent or LV M1 mcspc and a rapidly rising PSA (DT 12 mos)

18 Prostata: Malattia avanzata Roberto Iacovelli Update of previous trial LATITUDE trial, final OS analysis SPARTAN trial, PFS2 Outline: New data ARAMIS trial ARCHES trial CHEIRON trial Looking to the future ChekMate 650 Keynote-365 Genomic drivers of enzalutamide resistance AIOM Posta ASGO GU review Prostata, malattia avan

19 De Novo Presenting mcspc: De novo metastatic prostate cancer Presented By Karim Fizazi at 2017 ASCO Annual Meeting

20 Presented By Karim Fizazi at 2017 ASCO Annual Meeting, Published in NEJM

21 De Novo Presenting mcspc: Local RT (plus ADT) as a new Standard of Care for Initial Treatment? Presenting Low Vol. - mhspc mcspc STAMPEDE: Radiotherapy to the Primary Site improves OS in Low-Volume (oligomet?) newly diagnosed mcspc (prespecified subset analysis), but not in the unselected Population. STAMPEDE trial: multi-arm, multi-stage design Parker et al. Lancet 2018 Newly diagnosed mhspc N=2,061 (Jan 2013 Sep 2016) R 1:1 SOC (ADT ± DOC) (N=1,029) SOC (ADT ± DOC) + RT* to prostate (N=1,032) Primary endpoint: OS Two prespecified subgroup analyses: Baseline M+ Burden (CHAARTED criteria ) RT schedule *started 8 wk after R or DOC: RT weekly schedule (36 Gy/6 fr/6 wk) or RT daily schedule (55 Gy/20 fr/4 wk) High-volume Disease: visceral mets and/or 4 bone mets ( 1 outside vertebral column or pelvis) Pts imaged with CT scan/bone scan combinations (SOC) Secondary outcomes: FFS, PFS, M+ PFS, PCa-specific survival, and symptomatic local event-free survival Parker CC. ESMO 2018, abs LBA5 (data from oral presentation included)

22 LATITUDE Study, final OS analysis:

23 ARCHES Study: Initial Data

24 ARCHES Study: Initial Data

25 Presenting mcspc: new Standards of Care as Initial Treatment (DCT or ABI plus ADT) Presenting HR/HV mhspc mcspc ADT alone mcspc ADT plus Plus STAMPEDE Trials N Engl J Med Aug 20;373(8):737-46; Lancet Mar 19;387(10024):

26 mcrpc: CHEIRON Study:

27 ChekMate 650: ChekMate 650: ChekMate 650: Genomic drivers of enzalutamide resistance: AIOM Posta ASGO GU review Prostata, malattia avanzata. AIOM Posta ASGO GU review Prostata, malattia avanzata. AIOM Posta ASGO GU review Prostata, malattia avanzata. Roberto Iacovelli Roberto Iacovelli Roberto Iacovelli