Metastatic Castration Resistant Prostate Cancer Must we treat asymptomatic disease?

Avivit Peer

Oncology Institute

Rambam Health Care Campus

Haifa, Israel

Dis

eas

e B

urd

en

Castration

1st-line therapies

Local therapy

2nd-line hormonal therapy

2nd-line therapies

Disease continuum in prostate cancer

2

Asymptomatic

CRPC

Metastatic

Hormone-sensitive

Symptomatic

Time

Non-metastatic

HEIDENREICH A, ET AL. EUR UROL. 2013;64(2):260-265.

Additional therapies

Asymptomatic mcPCa Mild Symptomatic mcPCa Very Symptomatic mcPCa

Early vs Late treatment

A. Orsola. European Urology 2014

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Stratification into 2 groups:

• Group 1: asymptomatic/no pain (BPI-SF 0-1), PSA < 80 ng/mL and Gleason score < 8

– AA + P: 124/546 subjects (23%)

– P: 140/542 subjects (26%)

• Group 2: any of the following – mildly symptomatic mild pain (BPI-SF ≥ 2), PSA ≥ 80 ng/mL or Gleason score ≥ 8

– AA + P: 422/546 subjects (77%)

– P: 402/542 subjects (74%)

Miller K, et al. Poster (#775) presented at the 31st Annual EAU Congress, 11-15 March 2016, Munich, Germany

The Phase 3 COU-AA-302 Study of Abiraterone Acetate in Men With Chemotherapy-Naïve Metastatic Castration-Resistant Prostate Cancer: Stratified Analysis Based on

Pain, Prostate-Specific Antigen and Gleason Score

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AA + P Significantly Prolonged OS and rPFS versus P Alone in Groups 1 (asymptomatic, PSA < 80 GS < 8)

and Groups 2 (mildly symptomatic, PSA ≥ 80, GS ≥ 8)

Median OS Group 1 AA + P: 53.6 months P: 41.8 months HR=0.61 (95% CI: 0.43-0.87) p=0.0055

Median OS Group 2 AA + P: 31.2 months P: 28.4 months HR=0.84 (95% CI: 0.72-0.99) p=0.0321

Median rPFS Group 1 AA + P: 27.6 months P: 11.1 months HR=0.41 (95% CI: 0.30-0.57) p<0.0001

Median rPFS Group 2 AA + P: 13.7 months P: 8.2 months HR=0.59 (95% CI: 0.50-0.70) p<0.0001

Miller K, et al. Poster (#775) presented at the 31st Annual EAU Congress, 11-15 March 2016, Munich, Germany

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Time to Chemotherapy use and Time to Opiate use versus P Alone in Groups 1 and 2

Median time to chemotherapy use Group 1

AA + P: 37.0 months P: 24.3 months

HR=0.64 (95% CI: 0.46-0.89) p=0.0073

Median time to chemotherapy use Group 2

AA + P: 23.3 months P: 14.5 months

HR=0.71 (95% CI: 0.60-0.85) p=0.0001

Median time to opiate use Group 1

AA + P: NR P: 41.0 months

HR=0.69 (95% CI: 0.48-0.99) p=0.0409

Median time to opiate use Group 2

AA + P: 30.5 months P: 19.3 months

HR=0.70 (95% CI: 0.59-0.84) p=0.0001

Miller K, et al. Poster (#775) presented at the 31st Annual EAU Congress, 11-15 March 2016, Munich, Germany

WCDT

Presented By Scott Tomlins at 2015 ASCO Annual Meeting

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Presented By Robert Dreicer at 2015 ASCO Annual Meeting

Why Earlier?

- rPFS √

- OS √ - Time to chemotherapy √ - Time to opiate use √

So, how early is early enough?

M, 59, mCRPC

PSMA-PET/CT uptake in:

• Primary tumor in prostate

• Pelvic LNs (up to 12mm)

• Lytic lesions lt. pelvis & T6.

M, 65, Prostate Ca, Rising PSA Ga68 PSMA

LN metastases SUVmax 10.3

T9 vertebral met SUVmax 11.14

What is the real volume of the disease? Bone scan flare following initiation of NHT

1.2015 4.2015 06.2015

Background

Feb 2018

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SPARTAN Phase III study

Presented By Eric Small at 2018 Genitourinary Cancers Symposium

66 YM, CRPC , Rising PSA Negative bone scan, chest+abdomanal CT

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PROSPER Study Design

Subgroup Analysis of MFS

Time to PSA Progression

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