TERAGNOSIS Y NUEVAS DIANAS MOLECULARES EN CPRCm

Programa Multidisciplinar en Medicina nuclear

Madrid - H120: 13-14 de Noviembre de 2023

Therapeutic Sequencing in mCRPC

David Olmos MD PhD

Group leader Cancer Genetics & Genomics Group
Prostate Cancer & GU Cancer Program - Medical Oncology Department
IIS Hospital 12 de Octubre (I+12 )- Hospital Universitario 12 de Octubre
David Olmos MD PhD @Dolmos77
Classical Androgen Deprivation Therapy (ADT)

ADT
nmCRPC

Clinically Rising
mCRPC: mCRPC: mCRPC:
Localized PSA
1st line 2nd line Line X
Disease Noncastrate Clinical
Metastases:
De Novo Noncastrate

Hormone-naïve metastatic Metastatic castration- Abiraterone

prostate cancer resistant prostate cancer Enzalutamide
Docetaxel
Cabazitaxel
Ra-223

* Figure modified from Scher et al. J Clin Oncol 2016;34:1402-1418.

New indications beyond ADT (I)

* Figure modified from Scher et al. J Clin Oncol 2016;34:1402-1418.

nmCRPC

Clinically Rising
mCRPC: mCRPC: mCRPC:
Localized PSA
1st line 2nd line Line X
Disease Noncastrate Clinical
Metastases:
De Novo Noncastrate

Hormone-naïve metastatic Metastatic castration- Abiraterone

prostate cancer resistant prostate cancer Enzalutamide
Docetaxel
RDT in de- ADT+ : Cabazitaxel
novo low-risk Docetaxel Ra-223
disease Abiraterone Olaparib
Apalutamide Lu177-PSMA617
Enzalutamide
Doc+Abiraterone
New indications beyond ADT (II)ADT+ :
Apalutamide
Enzalutamide * Figure modified from Scher et al. J Clin Oncol 2016;34:1402-1418.
Darolutamide

High-risk: High-risk
nmCRPC
ADT+Abiraterone PSA Failure:
ADT+Enzalutamide
Clinically Rising
mCRPC: mCRPC: mCRPC:
Localized PSA
1st line 2nd line Line X
Disease Noncastrate Clinical
Metastases:
De Novo Noncastrate

Hormone-naïve metastatic Metastatic castration- Abiraterone

prostate cancer resistant prostate cancer Enzalutamide
Docetaxel
RDT in de- ADT+ : Cabazitaxel
novo low-risk Docetaxel Ra-223
disease Abiraterone Olaparib
Apalutamide Lu177-PSMA617
Enzalutamide
Doc+Abiraterone
How could we intregate all this changes in the CRPC
therapeutic scenario?

• Which are the current potential scenarios?

• Which treatments do we have in each scenario?
• Which evidence do we have for different sequences?
• Does the prior treatment scenario matters??
• Which clinical factors may be important?
• Is there any biological factors driving the decsision?
 Classical evolution towards mCRPC ADT +/- Vintage Hx

Classical setting mHSPC 🡪 PSA +/- Rx

nmCRPC 🡪 Rx

1st Line
mCRPC

PSA= PSA Progression; Rx= Radiographic progression

Current evolution towards mCRPC ADT +/- Vintage Hx

Classic settings mHSPC 🡪 PSA +/- Rx

nmCRPC 🡪 Rx

+High Risk🡪
Docetaxel 🡪 PD
PSA &/or Rx
1st Line +High-risk🡪
mCRPC mHSPC Docetaxel +Abi
/Daro🡪 PD Rx
Low/High risk 🡪
ARSi*🡪 PD Rx

*ARSi:
nmCRPC ARSi*🡪 PD Rx
Apalutamide
Darolutramide
Enzalutamide
nmHSPC ARSi*🡪 PD Rx
Abiraterone
PSA= PSA Progression; Rx= Radiographic progression
Are different scenarios molecularly?

Van Dessel et al. Nat Com 2019; Deek et al. Eur Urol 2021, Abida et al. JCPO 2017 8
 Enza o Abi
Which drugs could I use?
First line Docetaxel
mCRPC
mCRPC
PARPi+ARSi

Only prior ADT Common scene until recently, most trials run in this setting Radium 223

Cabazitaxel
mHSPC o
nmCRPC
First line First line First line
mCRPC 1L or 2L mCRPC
1L or 2L or 3L mCRPC
1L or 2L
after ADT + After ADT + ARSi
After ADT + ARSi* Docetaxel Enza o Abi Enza o Abi
Docetaxel + Docetaxel

Enza o ABI Docetaxel Docetaxel

Cabazitaxel Cabazitaxel Cabazitaxel

Olaparib
Radium 223 Radium 223
PARPi+/-ARSi
PARPi+ARSi
PARPi +/- ARSi PSMA-Lu177

PSMA-Lu177
*ARSi= Androgen Receptor Signalling inhbitor
 Enza o Abi
When can I use docetaxel?
Docetaxel
mCRPC
PARPi+ARSi

Only prior ADT Common scene until recently, most trials run in this setting Radium 223

Cabazitaxel
mHSPC o
nmCRPC
First line First line First line
mCRPC mCRPC mCRPC

after ADT + After ADT + ARSi

After ADT + ARSi* Docetaxel Enza o Abi Enza o Abi
Docetaxel + Docetaxel

Enza o ABI Docetaxel Docetaxel

Cabazitaxel Cabazitaxel Cabazitaxel

Olaparib
Radium 223 Radium 223
PARPi+/-ARSi
PARPi+ARSi
PARPi +/- ARSi PSMA-Lu177

PSMA-Lu177
*ARSi= Androgen Receptor Signalling inhbitor
 Enza o Abi
When can I use docetaxel?
First line Docetaxel
mCRPC
mCRPC
PARPi+ARSi

Only prior ADT Common scene until recently, most trials run in this setting Radium 223

Cabazitaxel
mHSPC o
nmCRPC
First line First line First line
mCRPC 1L or 2L mCRPC
1L or 2L or 3L mCRPC
1L or 2L
after ADT + After ADT + ARSi
After ADT + ARSi* Docetaxel Enza o Abi Enza o Abi
Docetaxel + Docetaxel

Enza o ABI Docetaxel Docetaxel

Cabazitaxel Cabazitaxel Cabazitaxel

Olaparib
Radium 223 Radium 223
PARPi+/-ARSi
PARPi+ARSi
PARPi +/- ARSi PSMA-Lu177

PSMA-Lu177
*ARSi= Androgen Receptor Signalling inhbitor
Docetaxel after ADT or after ABIRATERONE or ENZALUTAMIDe (ARSi)

• Pivotal studies of Docetaxel were conducted before ARSi era (Abiraterone or

Enzalutamide)
OS PFS PSA RR N Datos
12.5 m 4.4 - 5.1 m 26-55% 166 Real-life restrospective series
NR 3.0-7.6* m 40% 261 COU-AA-302 Post-hoc analysis
19.2 m NR 52.4% 1006 TAX-327
20.3 m 6.7 m 55% 75 (50 post)$ PROCAID (Phase II) Docetaxel
NR 8.3 m ---- 60 TRITON3 (Phase III) Docetaxel✚
• Time to porgression by PSA (n=100)
• $ pacientes post-abi, post-enza or both
• ✚ All BRCA1/2 or ATM mutant
Lorente et al. Lancet Oncol 2015, de Bono et al. Eur Urol 2017, Tannock et al. NEJM 2004, Crabb et al. JCO 2021; Fizazi et al. NEJM 2023
 Enza o Abi
Docetaxel after ADT or ADT+ARSi?
First line Docetaxel
mCRPC
mCRPC
PARPi+ARSi

Only prior ADT Common scene until recently, most trials run in this setting Radium 223

Cabazitaxel
mHSPC o
nmCRPC
First line First line First line
mCRPC 1L or 2L mCRPC
1L or 2L or 3L mCRPC
1L or 2L
after ADT + After ADT + ARSi
After ADT + ARSi* Docetaxel Enza o Abi Enza o Abi
Docetaxel + Docetaxel

Enza o ABI Docetaxel Docetaxel

Cabazitaxel Cabazitaxel Cabazitaxel

Olaparib
Radium 223 Radium 223
PARPi+/-ARSi
PARPi+ARSi
PARPi +/- ARSi PSMA-Lu177

PSMA-Lu177
*ARSi= Androgen Receptor Signalling inhbitor
Docetaxel after Docetaxel (Rechallenge)

• Multiple restrospectivce series which a wide range of reponses and contradictory

messages
• Data from post-hoc analysis in the GETUG 15 clinical trial

TTPP 1st-2nd
OS PSA RR N GETUG 15 post-Hoc
L
NR 6.0-6.6 45% 101, (80)* Docetaxel AFTER ADT alone
NR 4.1-3.4 14% 42, (29)* Docetaxel AFTER ADT-Doc
19.2 mo
* Evaluable NR
pts for PSA response 52.4% 1006 TAX-327

Lavaud et al. Eur Urol 2018, Tannock et al. NEJM 2004

 Enza o Abi
Docetaxel after ADT or 1 ARSi
First line Docetaxel
mCRPC
mCRPC
PARPi+ARSi

Only prior ADT Common scene until recently, most trials run in this setting Radium 223

Cabazitaxel
mHSPC o
nmCRPC
First line First line First line
mCRPC 1L or 2L mCRPC
1L or 2L or 3L mCRPC
1L or 2L
after ADT + After ADT + ARSi
After ADT + ARSi* Docetaxel Enza o Abi Enza o Abi
Docetaxel + Docetaxel

Enza o ABI Docetaxel Docetaxel

Cabazitaxel Cabazitaxel Cabazitaxel

Olaparib
Radium 223 Radium 223
PARPi+/-ARSi
PARPi+ARSi
PARPi +/- ARSi PSMA-Lu177

PSMA-Lu177
*ARSi= Androgen Receptor Signalling inhbitor
 Enza o Abi
When could we use an ARSi?
First line Docetaxel
mCRPC
mCRPC
PARPi+ARSi

Only prior ADT Common scene until recently, most trials run in this setting Radium 223

Cabazitaxel
mHSPC o
nmCRPC
First line First line First line
mCRPC 1L or 2L mCRPC
1L or 2L or 3L mCRPC
1L or 2L
after ADT + After ADT + ARSi
After ADT + ARSi* Docetaxel Enza o Abi Enza o Abi
Docetaxel + Docetaxel

Enza o ABI Docetaxel Docetaxel

Cabazitaxel Cabazitaxel Cabazitaxel

Olaparib
Radium 223 Radium 223
PARPi+/-ARSi
PARPi+ARSi
PARPi +/- ARSi PSMA-Lu177

PSMA-Lu177
*ARSi= Androgen Receptor Signalling inhbitor
ARSI after prior ADT or prior ADT and Docetaxel

• 2 pivotal studies showed efficacy of Abi and Enza, respectively, after Docetaxel+ADT
OS OS
N △OS HR RECIST Resp PSA Resp
(exp) (control)

COU-301: Abiraterona + P vs 14,8% vs 29,5% vs

Placebo + P 1195 15,8 m 11,2 m 3,4 m 0,74
3,3% 6%
AFFIRM: Enzalutamida vs Placebo 1199 18,4 m 13,6 m 4,8 m 0,63 29% vs 4% 54% vs 2%

• 2 pivotal studies showed efficacy of Abi and Enza, respectively, after ADT and prior to
docetaxel
OS rPFS Rx Resp PSA Resp N

32.4 mo Not reached 59% 78% 1717 PREVAIL

Not Reached 16.5 m 36% 62% 1088 COU-AA-302

De Bono et al, NEJM 2011. Scher et al 2012 ; Beer et al. NEJM 2014; Ryan et al. NEJM 2013
 Enza or Abi
When could we use an ARSi?
First line Docetaxel
mCRPC
mCRPC
PARPi+ARSi

Only prior ADT Common scene until recently, most trials run in this setting Radium 223

Cabazitaxel
mHSPC o
nmCRPC
First line First line First line
mCRPC 1L or 2L mCRPC
1L or 2L or 3L mCRPC
1L or 2L
after ADT + After ADT + ARSi
After ADT + ARSi* Docetaxel Enza or Abi Enza or Abi
Docetaxel + Docetaxel

Enza or ABI Docetaxel Docetaxel

Cabazitaxel Cabazitaxel Cabazitaxel

Olaparib
Radium 223 Radium 223
PARPi+/-ARSi
PARPi+ARSi
PARPi +/- ARSi PSMA-Lu177

PSMA-Lu177
*ARSi= Androgen Receptor Signalling inhbitor
ARSI after prior ADT and ARSi but prior to Docetaxel

• Limited evidence: ENZA after ABI better 🡪 PSA responses

OS PFS Resp Rx Resp PSA N

- 1,5 – 4,9 - 17-36% 187 retrosp. series ABI🡪ENZA

- 5.6 m - 1% 125 PLATO Phase II ENZA🡪ABI
- 5.7 m - 2% 126 PLATO Phase II ENZA🡪ENZ+ABI
- 1.3 m* - 4% 75 Vancouver Ph.2 ENZA🡪ABI
- 2.7 m* - 36% 73 Vancouver Ph.2 ABI🡪ENZA
NR 4.5m NR NR 41 TRITON3 (Phase 3) - 2° ARSI✚
NR 5.6 m 14.9% 20.4% 234 PSMAfore – 2° ARSI $
32.4 mo No alcanzado 59% 78% 1717 PREVAIL
No alcanzado 16.5 m 36% 62% 1088 COU-AA-302

✚ All BRCA1/2, $ PSMA positive

Noonan et al. Ann Oncol 2013; Loriot et al. Ann Oncol 2013; de Bono et al. NEJM 2011, Attard et al. JCO 2018, Khalaf et al. Lancet Oncol 2019;
Sternberg et al. Lancet Oncol 2014; Beer et al. NEJM ; Ryan et al. NEJM 2013; Fizazi et al. NEJM 20023; sartor et al.ESMO 2023
 Enza or Abi
If a 2nd ARSI enzalutamide after Abiraterone
First line Docetaxel
mCRPC
mCRPC
PARPi+ARSi

Only prior ADT Common scene until recently, most trials run in this setting Radium 223

Cabazitaxel
mHSPC o
nmCRPC
First line First line First line
mCRPC 1L or 2L mCRPC
1L or 2L or 3L mCRPC
1L or 2L
after ADT + After ADT + ARSi
After ADT + ARSi* Docetaxel Enza or Abi Enza or Abi
Docetaxel + Docetaxel

Enzalutamide Docetaxel Docetaxel

Cabazitaxel Cabazitaxel Cabazitaxel

Olaparib
Radium 223 Radium 223
PARPi+/-ARSi
PARPi+ARSi
PARPi +/- ARSi PSMA-Lu177

PSMA-Lu177
*ARSi= Androgen Receptor Signalling inhbitor
 Enza or Abi
After prior Doc and ARSi: 2nd ARSi or Cabazitaxel?
First line Docetaxel
mCRPC
mCRPC
PARPi+ARSi

Only prior ADT Common scene until recently, most trials run in this setting Radium 223

Cabazitaxel
mHSPC o
nmCRPC
First line First line First line
mCRPC 1L or 2L mCRPC
1L or 2L or 3L mCRPC
1L or 2L
after ADT + After ADT + ARSi
After ADT + ARSi* Docetaxel Enza or Abi Enza or Abi
Docetaxel + Docetaxel

Enzalutamide Docetaxel Docetaxel

Cabazitaxel Cabazitaxel Cabazitaxel

Olaparib
Radium 223 Radium 223
PARPi+/-ARSi
PARPi+ARSi
PARPi +/- ARSi PSMA-Lu177

PSMA-Lu177
*ARSi= Androgen Receptor Signalling inhbitor
ABI OR ENZA or CABAZITAXEL after prior ADT, ARSi and DOCETAXEL

De Wit et al. ESMO 2019. Abstract #LBA13. ; De Wit et al. N Eng J Med 2019
 Enza or Abi
Cabazitaxel better than 2nd ARSi after DOC+ARSi
First line Docetaxel
mCRPC
mCRPC
PARPi+ARSi

Only prior ADT Common scene until recently, most trials run in this setting Radium 223

Cabazitaxel
mHSPC o
nmCRPC
First line First line First line
mCRPC 1L or 2L mCRPC
1L or 2L or 3L mCRPC
1L or 2L
after ADT + After ADT + ARSi
After ADT + ARSi* Docetaxel Enza or Abi Enza or Abi
Docetaxel + Docetaxel

Enzalutamide Docetaxel Docetaxel

Cabazitaxel Cabazitaxel Cabazitaxel

Olaparib
Radium 223 Radium 223
PARPi+/-ARSi
PARPi+ARSi
PARPi +/- ARSi PSMA-Lu177

PSMA-Lu177
*ARSi= Androgen Receptor Signalling inhbitor
 Enza or Abi
Cabazitaxel after ADT+docetaxel or prior to docetaxel?
First line Docetaxel
mCRPC
mCRPC
PARPi+ARSi

Only prior ADT Common scene until recently, most trials run in this setting Radium 223

Cabazitaxel
mHSPC o
nmCRPC
First line First line First line
mCRPC 1L or 2L mCRPC
1L or 2L or 3L mCRPC
1L or 2L
after ADT + After ADT + ARSi
After ADT + ARSi* Docetaxel Enza or Abi Enza or Abi
Docetaxel + Docetaxel

Enzalutamide Docetaxel Docetaxel

Cabazitaxel Cabazitaxel Cabazitaxel

Olaparib
Radium 223 Radium 223
PARPi+/-ARSi
PARPi+ARSi
PARPi +/- ARSi PSMA-Lu177

PSMA-Lu177
*ARSi= Androgen Receptor Signalling inhbitor
CABAZITAXEL after OR prior to Docetaxel

• 2 pivotal randomized Phase III: TROPIC in mCRPC post-docetaxel and

FIRSTANA 1L Chemo in mCRPC

Cabazitaxel tras docetaxel OS OS

N △OS HR RECIST Resp PSA Resp
(exp) (control)

TROPIC: Cabazitaxel vs 39% vs

Mitoxantrona 755 15,1 m 12,7 m 2,4 m 0,70 14.4% vs 4.%
18%
Cabazitaxel 1ª línea de QT OS OS
N △OS HR RECIST Resp PSA Resp
(exp) (control)

TROPIC: Cabazitaxel vs 25.2 m 0,9 m 0.97 42% vs 32%* 57% vs 65%*

Docetaxel$ 1168 24.5 m* 24.3 m 0.2 m* 1.01* vs 31% vs 59%
$ <2% global exposition to prior Abi or Enza * CABA 20mg/m^2 arm

De Bono et al, Lancet 2010, Oudard et al. JCO 2017

 Enza or Abi
Cabazitaxel better after ADT+docetaxel +/- ARSi
First line Docetaxel
mCRPC
mCRPC
PARPi+ARSi

Only prior ADT Common scene until recently, most trials run in this setting Radium 223

Cabazitaxel
mHSPC o
nmCRPC
First line First line First line
mCRPC 1L or 2L mCRPC
1L or 2L or 3L mCRPC
1L or 2L
after ADT + After ADT + ARSi
After ADT + ARSi* Docetaxel Enza or Abi Enza or Abi
Docetaxel + Docetaxel

Enzalutamide Docetaxel Docetaxel

Cabazitaxel Cabazitaxel Cabazitaxel

Olaparib
Radium 223 Radium 223
PARPi+/-ARSi
PARPi+ARSi
PARPi +/- ARSi PSMA-Lu177

PSMA-Lu177
*ARSi= Androgen Receptor Signalling inhbitor
 Enza or Abi
Is a role for Ra223 in the mCRPC treatment sequence?
First line Docetaxel
mCRPC
mCRPC
PARPi+ARSi

Only prior ADT Common scene until recently, most trials run in this setting Radium 223

Cabazitaxel
mHSPC o
nmCRPC
First line First line First line
mCRPC 1L or 2L mCRPC
1L or 2L or 3L mCRPC
1L or 2L
after ADT + After ADT + ARSi
After ADT + ARSi* Docetaxel Enza or Abi Enza or Abi
Docetaxel + Docetaxel

Enzalutamide Docetaxel Docetaxel

Cabazitaxel Cabazitaxel Cabazitaxel

Ra223
Radium 223 Radium 223
PARPi+/-ARSi
PARPi+ARSi
PARPi +/- ARSi PSMA-Lu177

PSMA-Lu177
*ARSi= Androgen Receptor Signalling inhbitor
Ra223 after OR prior to Docetaxel

• pivotal randomised Phase III: ALSYMPCA

Parker et al. N Engl J Med 2013

 Enza or Abi
In theory Ra223 is indicated after or prior to docetaxel
First line Docetaxel
mCRPC
mCRPC
PARPi+ARSi

Only prior ADT Common scene until recently, most trials run in this setting Radium 223

Cabazitaxel
mHSPC o
nmCRPC
First line First line First line
mCRPC 1L or 2L mCRPC
1L or 2L or 3L mCRPC
1L or 2L
after ADT + After ADT + ARSi
After ADT + ARSi* Docetaxel Enza or Abi Enza or Abi
Docetaxel + Docetaxel

Enzalutamide Docetaxel Docetaxel

Cabazitaxel Cabazitaxel Cabazitaxel

Ra223
Radium 223 Radium 223
PARPi+/-ARSi
PARPi+ARSi
PARPi +/- ARSi PSMA-Lu177

PSMA-Lu177
*ARSi= Androgen Receptor Signalling inhbitor
 Enza or Abi
However ALSYMPCA TRIAL WAS PRE-aARSI ERA
First line Docetaxel
mCRPC
mCRPC
PARPi+ARSi

Only prior ADT Common scene until recently, most trials run in this setting Radium 223

Cabazitaxel
mHSPC o
nmCRPC
First line First line First line
mCRPC 1L or 2L mCRPC
1L or 2L or 3L mCRPC
1L or 2L
after ADT + After ADT + ARSi
After ADT + ARSi* Docetaxel Enza or Abi Enza or Abi
Docetaxel + Docetaxel

Enzalutamide Docetaxel Docetaxel

Cabazitaxel Cabazitaxel Cabazitaxel

Ra223
Radium 223 Radium 223
PARPi+/-ARSi
PARPi+ARSi
PARPi +/- ARSi PSMA-Lu177

PSMA-Lu177
*ARSi= Androgen Receptor Signalling inhbitor
Ra223 after ERA223 trial results

• ERA-223: AAP+Ra223 vs AAP+Placebo 🡪 An excess of death due fractures 🡪

EMA restricted RA223 use
...monotherapy or in combination with an LHRH analog for the treatment
of adult patients with mCRPC, symptomatic bone metastases and no
known visceral metastases, who are in progression after at least two
prior lines of systemic therapy for mCRPC (other than LHRH analogs),
or ineligible for any available systemic mCRPC treatment

Smith et al. Lancet Oncol 2018

 Enza or Abi
Ra223 post-ERA223
First line Docetaxel
mCRPC
mCRPC
PARPi+ARSi

Only prior ADT Common scene until recently, most trials run in this setting Radium 223

Cabazitaxel
mHSPC o
nmCRPC
First line First line First line
mCRPC 1L or 2L mCRPC
1L or 2L or 3L mCRPC
1L or 2L
after ADT + After ADT + ARSi
After ADT + ARSi* Docetaxel Enza or Abi Enza or Abi
Docetaxel + Docetaxel

Enzalutamide Docetaxel Docetaxel

Cabazitaxel Cabazitaxel Cabazitaxel

Radium 223
Radium 223 Radium 223
PARPi+/-ARSi
PARPi+ARSi
PARPi +/- ARSi PSMA-Lu177

PSMA-Lu177
*ARSi= Androgen Receptor Signalling inhbitor
 Enza or Abi
PARPi in combination or alone? Selected or unselected?
First line Docetaxel
mCRPC
mCRPC
PARPi+ARSi

Only prior ADT Common scene until recently, most trials run in this setting Radium 223

Cabazitaxel
mHSPC o
nmCRPC
First line First line First line
mCRPC 1L or 2L mCRPC
1L or 2L or 3L mCRPC
1L or 2L
after ADT + After ADT + ARSi
After ADT + ARSi* Docetaxel Enza or Abi Enza or Abi
Docetaxel + Docetaxel

Enzalutamide Docetaxel Docetaxel

Cabazitaxel Cabazitaxel Cabazitaxel

Radium 223
Radium 223 Radium 223
PARPi+/-ARSi
PARPi+ARSi
PARPi +/- ARSi PSMA-Lu177

PSMA-Lu177
*ARSi= Androgen Receptor Signalling inhbitor
 CAPTURE study cohort 1: mCRPC outcomes from first line

NOTE: naïve, non-adjusted, median survival outcomes

David Olmos MD PhD @Dolmos77 Olmos et al. ASCO 2023; Submitted for publication
 Enza or Abi
PSMA-Lu177 after or before chemotherapy?
First line Docetaxel
mCRPC
mCRPC
PARPi+ARSi

Only prior ADT Common scene until recently, most trials run in this setting Radium 223

Cabazitaxel
mHSPC o
nmCRPC
First line First line First line
mCRPC 1L or 2L mCRPC
1L or 2L or 3L mCRPC
1L or 2L
after ADT + After ADT + ARSi
After ADT + ARSi* Docetaxel Enza or Abi Enza or Abi
Docetaxel + Docetaxel

Enzalutamide Docetaxel Docetaxel

Cabazitaxel Cabazitaxel Cabazitaxel

Radium 223
Radium 223 Radium 223
PARPi+/-ARSi
PARPi+ARSi
PARPi +/- ARSi PSMA-Lu177

PSMA-Lu177
*ARSi= Androgen Receptor Signalling inhbitor
Some take home messages
MY VIEWS
OBVIUS FROM Ph2 and Ph3 trials
• Longitudinal image of the disease,
• Cabazitaxel is usually given after
consider sequences from the beggining
docetaxel > better than 2nd ARSi
• Count lines independently of stage
• Docetaxel seems better tan 2nd ARSi
• The best drug/combination as soon as
• If a 2nd ARSI better Enza after ABI
possible🡪 benefit usually 1L > 2L > 3L
• Radium is not indicated if nodes >3cm
• Toxicity vs efficacy / Comorbidities
or visceral MTS after 2L (or 1L)
• PARPi are more active in mut BRCA1/2
• Lu177-PSMA 🡪 Expression of PSMA