Cancer de la prostate: best of 2016

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1 Cancer de la prostate: best of 2016 Dr Christophe Massard GR2016, 3 DEC 2016

2 Disclosure Participation to advisory boards, speaker or investigator for: Amgen, Astellas, Astra Zeneca, Bayer, Celgene, Genentech, Ipsen, Jansen, Lilly, Novartis, Pfizer, Roche, Sanofi, Orion, MedImmune, New Oncology, DebioPharm

Disclosure Participation to advisory boards, speaker or investigator for: Amgen, Astellas, Astra Zeneca, Bayer, Celgene, Genentech, Ipsen, Jansen, Lilly, Novartis, Pfizer, Roche, Sanofi, Orion,

3 Disclosure Participation to advisory boards, speaker or investigator for: Amgen, Astellas, Astra Zeneca, Bayer, Celgene, Genentech, Ipsen, Jansen, Lilly, Novartis, Pfizer, Roche, Sanofi, Orion, MedImmune, New Oncology, DebioPharm I am a PI of Eli Lilly and Company trial with NOTCH inhibitor I will not discuss off label use in my presentation I will discuss investigational use in my presentation

4 Patient case 1: Presentation Age 48 years; Performance status 0 Presenting PSA 89.3 ng/ml RTUP; Gleason 8 (4+4) No symptoms Educational patient case

5 Be careful!!!

6 Some patients with metastatic hormone-sensitive prostate cancer may not be willing/are too frail to receive docetaxel

7 Patient case 1: Presentation Age 48 years; Performance status 0 Presenting PSA 89.3 ng/ml RTUP; Gleason 8 (4+4) with metastases LHRHa for 6 months; PSA nadir 5 ng/ml Bicalutamide added for PSA progression and no reponse Now PSA progression16.2 ng/ml Bone metastase and liver metastases Educational patient case

8 Patient case 1: best option? ADT+docetaxal ADT+Cabazitexal ADT+Arinhibitors (ABI/ENZA) ADT+RAD223

9 General recommendations in CRPC Check serum Testosterone (should be < 0,50 ng/ml) Imaging check up (bone scan + CT scan) Continue castration If prescribed, stop a androgen receptor antagonist («Withdrawal syndrome») Treat symptoms (bone RXT, TURP, anemia, etc) Discuss a new line of anti-cancer treatment

10 BE careful!!! Patient < 50 ans Castration <6 mois Liver metastases = NO ENZA/ABI

11 Patient case 1: Presentation Age 48 years; Performance status 0 Presenting PSA 89.3 ng/ml RTUP; Gleason 8 (4+4) LHRHa for 6 months; PSA nadir 5 ng/ml Bicalutamide added for PSA progression and no reponse Now PSA progression16.2 ng/ml Bone metastase and liver metastases Treatment with abiraterone And Palliative radiation to lumbar spine Educational patient case

12 Patient case 1: how to monitor? Blood test Physical examination every months Physical examination every 3 month Bone scan and CTscan

13 Patient case 1: Presentation Age 48 years; Performance status 0 Presenting PSA 89.3 ng/ml RTUP; Gleason 8 (4+4) LHRHa for 6 months; PSA nadir 5 ng/ml Bicalutamide added for PSA progression and no reponse Now PSA progression16.2 ng/ml Bone metastase and liver metastases Treatment with abiraterone At 3 months, PSA decrease after starting treatment with abiraterone PSA 2 ng/ml Educational patient case

14 Patient case 1: Presentation Age 48 years; Performance status 0 Presenting PSA 89.3 ng/ml RTUP; Gleason 8 (4+4) LHRHa for 6 months; PSA nadir 5 ng/ml Bicalutamide added for PSA progression and no reponse Now PSA progression16.2 ng/ml Bone metastase and liver metastases Treatment with abiraterone At 3 months, PSA decrease after starting treatment with abiraterone PSA 2 ng/ml And then INCREASE at 4 months 10ng/ml Educational patient case

15 Patient case 1: best option? ADT+docetaxal ADT+Cabazitexal ADT+Arinhibitors (switch to ENZA) ADT+RAD223

16 FIRSTANA: Study Design mcrpc and no prior chemotherapy N = 1,168 pts 159 centers worldwide R A N D O M I Z E CBZ 20 + PRED Cabazitaxel 20 mg/m² Q3W + prednisone 10 mg/d n = 389 CBZ 25 + PRED Cabazitaxel 25 mg/m² Q3W + prednisone 10 mg/d n = 388 DOC + PRED Docetaxel 75 mg/m² Q3W + prednisone 10 mg/d n = 391 Hypothesis: cabazitaxel is more effective than docetaxel in 1L mcrpc

17 Probability of overall survival (%) FIRSTANA: Overall Survival DOC + PRED CBZ 20 + PRED CBZ 25 + PRED Median OS, months (95% CI) DOC + PRED 24.3 ( ) CBZ 20 + PRED 24.5 ( ) CBZ 25 + PRED 25.2 ( ) CBZ 20 vs DOC HR ( ) P = CBZ 25 vs DOC HR 0.97 ( ) P = Number at risk DOC + PRED CBZ 20 + PRED CBZ 25 + PRED Time 197 (months) Docetaxel remains the standard for 1L chemotherapy

18 Proselica Hypothesis: Cabazitaxel 20 mg/m2 is non inferior to cabazitaxel 25 mg/m2

19 Proselica study CBZ 20 mg/m2 is non inferior to CBZ 25 mg/m2 and safer (and cheaper)

20 Robinson et al. Cell 2015

21 Que peut-on cibler? Robinson et al. Cell 2015

24 GGG

25 GGG

26 GGG

27 GGG CRPC post docetaxel trated with Ipilimumab+RTE

28 Ipilimumab in prostate cancer A trend but no evidence for better OS with ipi

32 MSI-H prostate cancer are not so rare (5%)

33 And progression? Identifier les candidats: Biomarqueurs 06/10/ /11/2015

34 Hyperprogressive disease (HPD): a new pattern of progression Champiat et al, Clin Cancer Res 2016

35 Hyperprogressive disease (HPD): a new pattern of progression Champiat et al, Clin Cancer Res 2016

36 Thank you

37 Thank you and discussion

GU Guidelines Update Meeting: M0 Castrate Resistant Prostate Cancer. Dr. Simon Yu Nov 18, 2017

GU Guidelines Update Meeting: M0 Castrate Resistant Prostate Cancer Dr. Simon Yu Nov 18, 2017 Faculty/Presenter Disclosure Faculty: Dr. Simon Yu Relationships with commercial interests: Grants/Research