ESMO VIRTUAL ADVANCED COURSE

ON CLINICAL QUESTIONS IN
PROSTATE CANCER
Metastatic Hormone Sensitive Prostate Cancer: State of
the Art Management in 2022

Fabio Schutz, MD
30-31 March 2022
DECLARATION OF INTERESTS

Research role (site Principal Investigator): Roche, BMS, MSD, Janssen,

Exelixis, AstraZeneca

Speaker’s bureau: Janssen, Bayer, Astellas, Zodiac, Astra Zeneca, MSD,

BMS, Roche

Advisory Board: Bayer, Astellas, Janssen, Zodiac, Astra Zeneca, Pfizer,

MSD, BMS

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IMPORTANCE OF PSA NADIR AT 7
MONTHS AFTER
IntrinsicADT
Resistance to ADT-Overall Survival in
mHSPC Patients by Nadir PSA
100% Median
At Risk Deaths in Months
≤ 0.2 602 199 75
80% >0.2 - ≤4 360 166 44
>4 383 322 13
P < .0001

60%

40%
PSA ≤ 02

20% 0.2 < PSA ≤ 4.0

PSA > 4.0

0%
0 24 48 72 96 120
Months After End of Induction
At Risk
Undetected 453 206 60
Normalized 213 72 19
Neither 91 17 7
. Oncol. 2006;24(24):3984-3990.
Hussain M, et al. J Clin
Hussain M, et al. J Clin Oncol 24:3984, 2006.

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PSA NADIR <0.2

Trial Control / ADT ADT + Docetaxel / ARI

CHAARTED 19.6% 32.0%
ARCHES 17.3% 68.1%
TITAN 28.7% 68.4%

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IMPORTANCE OF TESTOSTERONE
NADIR (NCIC PR-7 STUDY) (RETROSPECTIVE)

≤0.7nmol/L = ≤20ng/dL 0.7-1.7nmol/L = 20-50ng/dL ≥1.7nmol/L = ≥50ng/dL

Klotz L, et al. J Clin Oncol 33:1151, 2015.

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METASTATIC CSPC
DOCETAXEL TRIALS

Phase; Primary Results (Docetaxel Vs.

Trial Comparator
n Endpoint Comparator)
GETUG-AFU15 3 mOS: 58.9 vs 54.2m
ADT OS
(2013) N=385 HR 1.01 (p=ns)
3 mOS 57.6vs 44m
CHAARTED (2015) ADT OS
N=790 HR 0,61 (p<0.001)
ADT (+ 3 mOS 81 vs 71m
STAMEPEDE (2016) OS
Zoledronic acid) N=1776 HR 0.78 (p=0.006)

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 METASTATIC CSPC
NEW HORMONAL AGENTS TRIALS
Compara Primary Treatment Vs. Control;
Trial Population Phase; n
tor Endpoint HR (95% CI)
LATITUDE, ADT + 3 mOS: 53.3 vs. 36.5m
mCSPC OS
2017 Placebo N=1199 HR 0.66 (0.56-0.78)
Abi.
STAMPEDE, mCSPC, locally ADT 3 3y OS: 83% vs. 73%
OS
2017 advanced PCa alone N=1917 HR 0.63 (0.52-0.76)
ENZAMET, ADT + 3 3y OS: 80% vs. 72%
mCSPC OS
2019 anti-andr. N=1125 HR 0.67 (0.52-0.86)
Enza.
ARCHES, ADT + 3 3y OS: 78% vs. 69%
mCSPC OS
2021 Placebo N=1150 HR 0.66 (0.53-0.81)
ADT + 3 2y OS: 82.4% vs. 73.5%
Apa. TITAN, 2021 mCSPC OS
Placebo N=1052 HR 0.65 (0.53-0.79)
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DE NOVO MCSPC IS ASSOCIATED
WITH A WORSE OUTCOME

Francini E, et al. The Prostate 2018;78:889-95.

Fabio Schutz, MD Content of this presentation is copyright and responsibility of the author. Permission is required for re-use.
CAUTION WHEN DOING INDIRECT COMPARISONS
AS THE POPULATION ARE NOT BE THE SAME

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STAMPEDE TRIAL
Abiraterone Vs. Docetaxel

Overall Survival Metastatic PFS PFS

Failure Free Survival (PSA First SRE

driven)

Sydes MR, et al. Ann Oncol 29:1235, 2018.

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TRIPLE THERAPY – PEACE-1
SOC (ADT +/- Docetaxel) +/- Abiraterone
rPFS
Overall population Docetaxel population
SOC (ADT +/- Docetaxel +/- RT) SOC (ADT + Docetaxel +/- RT)

Fizazi K, et al. ASCO 2021 and ESMO 2021

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TRIPLE THERAPY – PEACE-1
SOC (ADT +/- Docetaxel) +/- Abiraterone
rPFS by metastatic burden

Fizazi K, et al. ASCO 2021 and ESMO 2021

Fabio Schutz, MD Content of this presentation is copyright and responsibility of the author. Permission is required for re-use.
TRIPLE THERAPY – PEACE-1
SOC (ADT +/- Docetaxel) +/- Abiraterone
OS
Overall population Docetaxel population
SOC (ADT +/- Docetaxel +/- RT) SOC (ADT + Docetaxel +/- RT)

Fizazi K, et al. ASCO 2021 and ESMO 2021

Fabio Schutz, MD Content of this presentation is copyright and responsibility of the author. Permission is required for re-use.
TRIPLE THERAPY – PEACE-1
SOC (ADT + Docetaxel) +/- Abiraterone
OS by metastatic burden

Fizazi K, et al. ASCO 2021 and ESMO 2021

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TRIPLE THERAPY – ARASENS
ADT + Docetaxel +/- Darolutamide/Placebo

Smith MR, et al. ASCO GU 2022.

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QUALITY OF LIFE
LATITUDE – Abiraterone Vs. Placebo

Chi KN, et al. Lancet Oncol 19:194; 2018.

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QUALITY OF LIFE
ENZAMET – Enzalutamide Vs. Placebo

Stockler M, et al. ESMO 2019.

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QUALITY OF LIFE
ARCHES – Enzalutamide Vs. Placebo

Stenzl A, et al. Eur Urol 78:603; 2020.

Fabio Schutz, MD Content of this presentation is copyright and responsibility of the author. Permission is required for re-use.
QUALITY OF LIFE
ARCHES – Enzalutamide Vs. Placebo

Stenzl A, et al. Eur Urol 78:603; 2020.

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QUALITY OF LIFE
TITAN – Apalutamide Vs. Placebo

Stenzl A, et al. Eur Urol 78:603; 2020.

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RAPID CHANGING LANDSCAPE
ESMO Guidelines (June 2020)

• This will probably be updated

soon to include ADT + Docetaxel
+ Abi or Daro for those with high-
risk / high-volume disease

• ADT + Docetaxel alone will

probably not be considered na
option for mCSPC

• ADT + Darolutamide may be

added as an option as weel

Parker C, et al. Ann Oncol 31:1119, 2020

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CONCLUSIONS

• If available, ARIs (i.e. Abi, Enza, Apa and Daro) in combination with
ADT should be the preferred option in mCSPC
Docetaxel is less effective than Abiraterone (at least in short term
•

endpoints) (STAMPEDE), and should not be used alone anymore

(PEACE-1 and STAMPEDE), unless there is no access to ARIs
Some patients with recurrent mCSPC (post RP or RT) may not
•

need ARIs
Consider different AEs profile, experience and access to choose
•

which ARIs
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CONCLUSIONS

• Docetaxel should (usually) be reserved for the following situations:

Patients with high-volume / high-risk disease
•

Patients with De novo metastatic disease

•

Docetaxel should be combined with Abi (PEACE-1) or Daro

•

(ARASENS)
• Triple therapy trials evaluated the benefit of adding ARI, and did not
evaluate the benefit of adding docetaxel to ADT + ARI

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