METASTATIC PROSTATE CANCER

An ever longer journey?

Dr Christoph Oing
Dept. of Oncology, Haematology and BMT
University Medical Center Eppendorf
Hamburg, Germany

Member of the ESMO Young Oncologist Committee

DISCLOSURE INFORMATION
Personal financial interests
Honoraria:
• Speaker: Medac, Ipsen, Roche
• Advisory role: Bayer
Stock ownership: None
Direct research funding: Roche, PharmaMar

Institutional financial interests None

Non-financial interests
• Non-remunerated activities
ESMO YOC and RTF member, ESMO YOC
representative of EMUC scientific committee,
chariman of the DGHO Young Oncologists,
GTCSG representative, EORTC GUCG &
STBSG member
CASE PRESENTATION
Primary diagnosis
DIAGNOSIS & PATIENT HISTORY
Case presentation
Age: 59
06/2017 Diagnosis of primary bone metastatic prostatic adenocarcinoma
♦ Gleason 4+4=8, ISUP GG 4
♦ PSA 72.4 µg/L
♦ cT2b cN0 cM1b (axial skeleton with at least 5 lesions and metastasis to the femur)
♦ High volume (LATTITUDE): ≥3 bone lesions, ISUP GG ≥4
♦ High burden (CHAARTED2): ≥4 bone lesions incl. ≥1 non-vertebral/pelvic
Comorbidities:
♦ Mild hypertension
Family history:
♦ Mother succumbing to Breast Cancer aged 40

1 Fizazi et al., NEJM 2017; 377:352-60 2 Sweeney et al., NEJM 2015; 373:737-46
CASE PRESENTATION
Primary treatment - mHSPC
PRIMARY TREATMENT
mHSPC treatment starting 06/2017 ARCHES study design

Key eligibility criteria

• mHSPC
• ECOG 0-1 ENZA 160mg/d +
N = 1.150
• ADT <3mos unless ADT
prior DOCE (≤ 6mos)
R 1:1
Stratification factors
• Disease volume Placebo + ADT
(low vs. high)
• Prior DOCE for mHSPC
(none, 1-5x, 6x)
Primary endpoint
• rPFS: time form R to first objective evidence of radiographic
progression, or death from any cause within 24 weeks of treatment
discontinuation, whichever occurs first

Armstrong AJ, et al. ASCO GU 2019.

CASE PRESENTATION
Subsequent treatment - mCRPC
SYSTEMIC TREATMENT
mCRPC treatment starting 03/2018

Abiraterone/P Enzalutamide Carbo / Cabazitaxel Taxol / Ifosfamide

Start 03/2018 04/2019 07/2020 10/2020
N cycles 12 14 4 2
PSA nadir [µg/L] 2.5 14.2 35.5 (prior cycle 1) 60.4 (prior cycle 1)
Radiographic response PR SD PD PD

Additional local treatment:

⬧ 01/2019 Palliative EBRT hip and proximal femoral bone (15 MeV, 13x 3Gy fractions)
 TREATMENT SUMMARY

06/2017 03/2018 04/2019 07/2020 11/2020 12/2020 03/2021

Hormonal
status mHSPC mCRPC

Treatment
LHRH + ARCHES ABIRATERONE/ ENZALUTAMIDE CABAZITAXEL/ TAXOL/
DOCETAXEL x5 placebo arm PREDNISONE CARBOPLATIN IFOSFAMIDE

DENOSUMAB

210
Total PSA [µg/L] (ULN < 4.0)

110

90 73.8
72.4 60.4
70

50
40.4
35.5
30
10.6 14.2
1.4 5.6 2.5
10

time
 TREATMENT SUMMARY

06/2017 03/2018 04/2019 07/2020 11/2020 12/2020 03/2021

Hormonal
status mHSPC mCRPC

LHRH + ARCHES ABIRATERONE/ ENZALUTAMIDE CABAZITAXEL/ TAXOL/

Treatment
DOCETAXEL x5 placebo arm PREDNISONE CARBOPLATIN IFOSFAMIDE ?
DENOSUMAB

210
Total PSA [µg/L] (ULN < 4.0)

40
34.8

NSE [µg/L] (ULN - 18.3)

110
33.5
29.0 30
90 73.8
72.4 60.4
70
18.6 25.2 20

50
40.4 20.6
35.5
30
10.6 14.2 15.8 10
12.8
1.4 5.6 2.5
10

time
 TURP OF THE PROSTATIC PRIMARY AT PROGRESSION
Immunohistochemical study Nov 2020

Gleason 4 pattern Gleason 5 pattern

Strong membraneous
Strong AR expression
PSMA staining
MOLECULAR TESTING
Illumina HiSeq 500
◆ 08/2020 TURP for fresh tissue sampling
◆ WES and TMB assessment
◆ TMB: 7.06 / mb (non-synonymous mutations)

Gene Mutation Allele frequency [%] Functional annotation

JAK3 p.Val722Ile 50.3 Likely activating
RANBP2 p.Val966fs*31 4.5 Deleterious
PAX8 p.Gln354* 31.6 Deleterious
NCOR1 p.Gln978* 40.5 Deleterious
BRCA2 p.Met1Ile 70.5 Deleterious
TP53 p.Arg249Ser 42.2 Likely deleterious
TMPRSS:ERG Fusion gene
 TREATMENT SUMMARY

06/2017 03/2018 04/2019 07/2020 11/2020 12/2020 03/2021

Hormonal
status mHSPC mCRPC

Treatment
LHRH + ARCHES ABIRATERONE/ ENZALUTAMIDE CABAZITAXEL/ TAXOL/ OLAPARIB
DOCETAXEL x5 placebo arm PREDNISONE CARBOPLATIN IFOSFAMIDE

DENOSUMAB

210
Total PSA [µg/L] (ULN < 4.0)

40
34.8

NSE [µg/L] (ULN - 18.3)

110
33.5
29.0 30
90 73.8
72.4 60.4
70
18.6 25.2 20

50
40.4 20.6
35.5
30
10.6 14.2 15.8 10
12.8
1.4 5.6 2.5
10

time
 TREATMENT SUMMARY

06/2017 03/2018 04/2019 07/2020 11/2020 12/2020 03/2021

Hormonal
status mHSPC mCRPC

Treatment
LHRH + ARCHES ABIRATERONE/ ENZALUTAMIDE CABAZITAXEL/ TAXOL/ OLAPARIB
DOCETAXEL x5 placebo arm PREDNISONE CARBOPLATIN IFOSFAMIDE

DENOSUMAB
218.2
210
Total PSA [µg/L] (ULN < 4.0)

40
34.8 90.8

NSE [µg/L] (ULN - 18.3)

110
33.5
29.0 30
90 73.8
72.4 60.4
70
18.6 25.2 20

50
40.4 20.6
35.5
30
10.6 14.2 15.8 10
12.8
1.4 5.6 2.5
10

time
 TREATMENT SUMMARY

06/2017 03/2018 04/2019 07/2020 11/2020 12/2020 03/2021

Hormonal
status mHSPC mCRPC

LHRH + ARCHES ABIRATERONE/ ENZALUTAMIDE CABAZITAXEL/ TAXOL/ OLAPARIB

Treatment
DOCETAXEL x5 placebo arm PREDNISONE CARBOPLATIN IFOSFAMIDE ?
DENOSUMAB
218.2
210
BRCA2mut
Total PSA [µg/L] (ULN < 4.0)

40
34.8 90.8

NSE [µg/L] (ULN - 18.3)

110
33.5
NSE ↑ 29.0 30
90 73.8

70
72.4 Castration resistance 60.4
18.6 25.2 20

50
40.4 20.6
35.5
30
10.6 14.2 15.8 10
12.8
1.4 5.6 2.5
10

time
DISCUSSION QUESTIONS
Optimal management of mHSPC and mCRPC

◆ Intensified first-line treatment – What, when and for whom?

◆ Disease burden according to LATTITUDE or CHAARTED?
◆ Treatment sequencing in mCRPC?
◆ When to suspect neuroendocrine disease and how to treat it?
◆ When to test for HRR aberrations?
◆ What to test for? Germline or somatic? BRCA1/2 / ATM / PALB2 / etc.?
◆ Resistance mechanisms to PARPi?
Dr Christoph Oing
Dept. Of Oncolgoy, Haematology and BMT
University Medical Center Eppendorf
Hamburg, Germany
Email: c.oing@uke.de

Contacts ESMO

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esmo@esmo.org

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