Carcinoma della Prostata: Malattia localizzata e localmente avanzata

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1 Carcinoma della Prostata: Malattia localizzata e localmente avanzata Salvatore Siena Ospedale Niguarda Ca Granda, Milano Riccardo Ricotta

2 Disclosures Honoraria from Astellas Pharma, Bayer, BMS, Janssen Oncology, Novartis, Pfizer, Sanofi-Genzyme Advisor roles for Janssen Oncology, Novartis, Sandoz, Sanofi-Genzyme

3 Abstracts

4 Highlights New treatment options for nmcrpc Imaging PET for primary or recurrent PCa «Modern» neoadjuvant therapy Immunotherapy for CSPC

5 Highlights New treatment options for nmcrpc Imaging PET for primary or recurrent PCa «Modern» neoadjuvant therapy Immunotherapy for CSPC

6 ARAMIS: Efficacy and safety of darolutamide in nonmetastatic castration-resistant prostate cancer Presented By Karim Fizazi at 2019 Genitourinary Cancers Symposium

7 Background: next-generation androgen receptor inhibitors Presented By Karim Fizazi at 2019 Genitourinary Cancers Symposium

8 ARAMIS trial design Presented By Karim Fizazi at 2019 Genitourinary Cancers Symposium

9 ARAMIS endpoints Presented By Karim Fizazi at 2019 Genitourinary Cancers Symposium

10 Baseline patient characteristics Presented By Karim Fizazi at 2019 Genitourinary Cancers Symposium

11 Primary endpoint: Metastasis-free survival 59% risk reduction of distant metastases or death Presented By Karim Fizazi at 2019 Genitourinary Cancers Symposium

12 MFS benefit was consistent across subgroups Presented By Karim Fizazi at 2019 Genitourinary Cancers Symposium

13 Secondary endpoint: Overall survival 29% risk reduction of death Presented By Karim Fizazi at 2019 Genitourinary Cancers Symposium

14 Secondary endpoints Presented By Karim Fizazi at 2019 Genitourinary Cancers Symposium

15 Incidence of TEAEs Presented By Karim Fizazi at 2019 Genitourinary Cancers Symposium

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

17 Health-related quality of life outcomes Presented By Karim Fizazi at 2019 Genitourinary Cancers Symposium

18 Slide 20 N Engl J Med 2019 Presented By Karim Fizazi at 2019 Genitourinary Cancers Symposium

19 Updated Analysis of Progression-Free Survival With First Subsequent Therapy and Safety in the SPARTAN Study of Apalutamide in Patients With High-Risk Nonmetastatic Castration-Resistant Prostate Cancer Presented By Eric Small at 2019 Genitourinary Cancers Symposium

20 SPARTAN Randomized, Phase 3, Placebo-Controlled Trial Presented By Eric Small at 2019 Genitourinary Cancers Symposium

21 SPARTAN Randomized, Phase 3, Placebo-Controlled Trial 1 Year Later Presented By Eric Small at 2019 Genitourinary Cancers Symposium

22 Slide 4 Presented By Eric Small at 2019 Genitourinary Cancers Symposium

23 Slide 6 Presented By Eric Small at 2019 Genitourinary Cancers Symposium

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

25 Slide 8 Presented By Eric Small at 2019 Genitourinary Cancers Symposium

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

27 Slide 10 Presented By Eric Small at 2019 Genitourinary Cancers Symposium

28 Basal-Luminal Status is Associated with Response to Apalutamide Decipher GC score Presented By Felix Feng at 2019 Genitourinary Cancers Symposium

29 Basal-Luminal Status is Associated with Response to Apalutamide Presented By Felix Feng at 2019 Genitourinary Cancers Symposium

31 Conclusions All pts benefit from the addition of APA to ADT, regardless DECIPHER GC score Half of men had a high DECIPHER GC score, indicating aggressive disease and hisk risk of developing metastases. These pts may be a good candidate for early treatment intensification The magnitude of benefit with APA + ADT was greater among pts with luminal subtype Subtyping by basal/luminal signature may be an effective approach for pts selection in clinical studies

32 Highlights New treatment options for nmcrpc Imaging PET for primary or recurrent PCa «Modern» Neoadjuvant therapy Immunotherapy for CSPC

33 A randomised trial comparing Fluorocholine-PET/CT with Conventional Imaging in primary or recurrent prostate cancer Presented By Scott Williams at 2019 Genitourinary Cancers Symposium

34 -The primary endpoint was to determine whether FCH was more effective as a FLI approach in changing management (from radical to palliative intent or the reverse) Design Considerations -Secondary endpoints included incremental utility of SLI and negative predictive value (NPV) based on PFS Presented By Scott Williams at 2019 Genitourinary Cancers Symposium FCH = 18 Flourocholine-PET/CT FLI = first-line imaging SLI = second-line imaging

35 Slide 9 High-impact management changes occurred in 27.8% of FCH cases vs 11.1% in the CIm arm (p=0.032) Presented By Scott Williams at 2019 Genitourinary Cancers Symposium

36 Slide 10 Presented By Scott Williams at 2019 Genitourinary Cancers Symposium

37 Negative Predictive Value Freedom from progression (FFP) = time during which the patient was free from cancer progression Presented By Scott Williams at 2019 Genitourinary Cancers Symposium

38 Negative Predictive Value Presented By Scott Williams at 2019 Genitourinary Cancers Symposium

39 Conclusions Presented By Scott Williams at 2019 Genitourinary Cancers Symposium

40 Highlights New treatment options for nmcrpc Imaging PET for primary or recurrent PCa «Modern» neoadjuvant therapy Immunotherapy for CSPC

41 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 Neoadjuvant ADT + Enzalutamide for 6 mos in 33 pts with newly diagnosed, high-risk PC - Pts underwent 2 mpmri: baseline and post 6 mos of therapy. Post-trt mpmri was followed by RP - Primary endpoint: feasibility of mpmri for localization and detection of PC before and after therapy Results: - Median baseline and post therapy PSA = 9.58 and <0.02, respectively. No pt was taken off-trt for AE - Using RCB <0.05 cc, 12 pts had minimal residual disease of which 4 pts had pathologic complete response - Post-trt mpmri volume correlated with final pathology in all cases RCB = residual cancer burden

42 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 RCB RCB = residual cancer burden

43 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 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 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

peg-filgrastim x 6 cycles) vs Arm B (AA/P + LHRH) for 6 months prior to RP - The primary objective is to compare the

44 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)

45 Highlights New treatment options for nmcrpc Imaging PET for primary or recurrent PCa «Modern» Neoadjuvant therapy Immunotherapy for CSPC

46 A phase II study of nivolumab in patients with high-risk biochemically recurrent (BCR) prostate cancer (PCa) Einstein DJ, et al. Abstr #TPS341)

A randomized phase Ib/II study of nivolumab with or without BMS-986253 in combination with a short course of ADT in men with

47 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)

48 Take home message Nuove opzioni per il trattamento del nmcrpc Potenziali criticità: - Quale farmaco per quali pazienti - End-points degli studi - Impatto sulla biologia tumorale e sulle strategie di sequencing - Ruolo dell imaging Imaging PET: indicazioni e potenziale ruolo nella pratica clinica ancora da definire Terapia neoadiuvante e immunoterapia per la malattia ormonosensibile: nuove opzioni in corso di studio, sono state riportate solo evidenze preliminari e non trasferibili nella pratica clinica

49 Grazie per l attenzione riccardo.ricotta@ospedaleniguarda.it

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

Sergio Bracarda MD, Medical Oncology, Dept. Of Oncology Az. Ospedaliera S. Maria, Terni; Italy Milano, 2 marzo 2019 My Disclosure Adv. Board Member for: Pfizer, BMS, Novartis, MSD, Roche, Genentech, Astellas,