ARCHES – the role of androgen deprivation therapy (ADT) with enzalutamide (ENZA) or placebo (PBO) in metastatic hormone-sensitive prostate cancer (...

Date 30 September 2019
Event ESMO 2019 Congress
Session Poster Display session 3
Topics Prostate Cancer
Presenter Arnulf Stenzl
Citation Annals of Oncology (2019) 30 (suppl_5): v325-v355. 10.1093/annonc/mdz248
Authors A. Stenzl1, R.Z. Szmulewitz2, D.P. Petrylak3, J. Holzbeierlein4, A. Villers5, A.A. Azad6, A. Alcaraz7, B.Y. Alekseev8, T. Iguchi9, N.D. Shore10, B. Rosbrook11, B. Baron12, G.P. Haas13, R. Morlock14, K. Ramaswamy15, A.J. Armstrong16
  • 1Dept. Of Urology, Eberhard Karls University, 72076 - Tübingen/DE
  • 2Medical Oncology, The University of Chicago, 60653 - Chicago/US
  • 3Medical Oncology, Yale Cancer Center, 06510 - New Haven/US
  • 4Department Of Urology, The University of Kansas Medical Center, 66103 - Kansas City/US
  • 5Department Of Urology, University Hospital Centre, Lille University, 59000 - Lille/FR
  • 6Medical Oncology, Monash Health, 3168 - Melbourne/AU
  • 7Urology, Hospital Clinic de Barcelona, 08036 - Barcelona/ES
  • 8Oncology, Hertzen Moscow Cancer Research Institute, 125284 - Moscow/RU
  • 9Urology, Osaka City University Graduate School of Medicine, 558-8585 - Osaka/JP
  • 10Medical Oncology, Carolina Urologic Research Center, Myrtle Beach/US
  • 11Clinical Statistics, Pfizer Inc., 92121 - San Diego/US
  • 12Statistics, Astellas Pharma Inc., 2333 BE - Leiden/NL
  • 13Global Medical Affairs, Astellas Pharma Inc., 60062 - Northbrook/US
  • 14Heor, Astellas Pharma Inc., 60062 - Northbrook/US
  • 15Heor, Pfizer Inc., 10017 - New York/US
  • 16Duke Cancer Institute Center For Prostate And Urologic Cancers, Duke University, 27710 - Durham/US

Abstract

Background

ENZA, a potent androgen receptor inhibitor, provides benefit in men with castration-resistant prostate cancer (CRPC). In post hoc analyses, the role of ENZA + ADT in mHSPC patients (pts) randomized within the multinational, double-blind, PBO-controlled, Phase 3 ARCHES study (NCT02677896) was determined by disease volume and risk group stratification.

Methods

mHSPC pts were randomized 1:1 to ENZA (160 mg/day) + ADT or PBO + ADT. The primary endpoint was radiographic progression-free survival (rPFS). Secondary endpoints included prostate-specific antigen (PSA) progression and radiographic responses, overall survival (OS), and quality of life (QoL). Analyses were completed by CHAARTED-defined disease volume and LATITUDE-defined risk groups.

Results

1150 pts were randomized (ENZA + ADT, n = 574; PBO + ADT, n = 576). Median follow-up was 14.4 months. ENZA + ADT significantly improved rPFS (hazard ratio [95% CI] 0.39 [0.30, 0.50]; p < 0.0001). ENZA + ADT pts significantly benefited from prolonged rPFS in all subgroups (Table). Significant treatment benefits were observed with ENZA + ADT in several secondary clinical endpoints in the overall population and in both high and low disease volume and risk groups (Table). High QoL at baseline was maintained over time. OS data are immature. Adverse events (AEs) were reported in 85.1% of ENZA + ADT vs. 85.9% of PBO + ADT pts, with no unexpected AEs.Table:

853P

Overall (n = 1150)Low-volume diseasea (n = 423)High-volume diseasea (n = 727)Low riskb (n = 556)High riskb (n = 511)
HR (95% CI)c
Primary endpoint
rPFSd0.39 (0.30, 0.50)0.25 (0.14, 0.46)0.43 (0.33, 0.57)0.42 (0.28, 0.62)0.34 (0.25, 0.47)
Secondary endpoints
Time to PSA progression0.19 (0.13, 0.26)0.08 (0.03, 0.20)0.22 (0.16, 0.32)0.14 (0.08, 0.25)0.21 (0.14, 0.31)
Time to castration resistance0.28 (0.22, 0.36)0.18 (0.10, 0.32)0.32 (0.24, 0.41)0.27 (0.18, 0.39)0.27 (0.20, 0.37)
Time to first SSE0.52 (0.33, 0.80)0.25 (0.07, 0.91)0.59 (0.37, 0.95)0.39 (0.19, 0.81)0.56 (0.32, 0.98)
Time to new antineoplastic therapy0.28 (0.20, 0.40)0.39 (0.18, 0.82)0.27 (0.18, 0.40)0.28 (0.16, 0.50)0.28 (0.18, 0.43)
Rate difference (95% CI)e
PSA undetectable (<0.2 ng/mL) rate,f %50.5 (45.3, 55.7)48.4 (39.3, 57.4)50.7 (44.5, 57.0)54.7 (47.2, 62.1)46.0 (38.5, 53.5)
ORR,f %19.3 (10.4, 28.2)21.1 (5.0, 37.3)18.6 (7.9, 29.3)16.4 (2.9, 29.9)21.7 (9.8, 33.5)
a

Defined as per CHAARTED trial criteria; high volume is defined as the presence of visceral metastases or ≥ 4 bone lesions with ≥1 beyond the vertebral bodies and pelvis (Sweeney et al, New Engl J Med 2014); 

b

Defined as per LATITUDE trial criteria; high-risk patients had ≥2 of the following: Gleason score of ≥ 8 (scale of 2–10), ≥3 bone lesions and/or the presence of measurable visceral metastasis (Fizazi et al, New Engl J Med 2017); 

c

HR < 1 favors ENZA + ADT; HR > 1 favors PBO + ADT; 

d

Assessed by ICR or death within 24 weeks of treatment discontinuation; 

e

Difference >0 favors ENZA + ADT; difference <0 favors PBO + ADT; 

f

Of those with detectable PSA or measurable disease at baseline, respectively. ADT=androgen deprivation therapy; CI=confidence interval; ENZA=enzalutamide; HR=hazard ratio; ICR=independent central review; PBO=placebo; PSA=prostate-specific antigen; ORR=objective response rate; OS=overall survival; QoL=quality of life; rPFS=radiographic progression free survival; SSE=symptomatic skeletal event.

Conclusions

ENZA + ADT treatment showed efficacy benefit across all mHSPC pts, irrespective of disease volume and risk group. Similar delays in rPFS, symptomatic skeletal events, PSA progression, castration resistance, and improvements in radiographic responses and PSA declines, with maintenance of high QoL over time, were observed. Preliminary safety analysis appears consistent with the safety profile of ENZA in previous CRPC clinical trials.

Clinical trial identification

NCT02677896.

Editorial acknowledgement

Beatrice Vetter-Ceriotti and Lauren Smith from Complete HealthVizion, funded by the study sponsors.

Legal entity responsible for the study

Astellas Pharma Inc. and Medivation LLC, a Pfizer Company, the co-developers of enzalutamide.

Funding

Astellas Pharma Inc. and Medivation LLC, a Pfizer Company, the co-developers of enzalutamide.

Disclosure

A. Stenzl: Advisory / Consultancy: Bipsen Pharma; Advisory / Consultancy: Roche; Advisory / Consultancy, Research grant / Funding (self), Travel / Accommodation / Expenses: Janssen; Advisory / Consultancy: Alere; Advisory / Consultancy: BMS; Advisory / Consultancy: Stebatiotechnology; Research grant / Funding (self): Karl Storz AG; Research grant / Funding (self): Astellas Pharma; Research grant / Funding (self): AstraZeneca; Research grant / Funding (self): Medivation; Travel / Accommodation / Expenses: Ipsen Pharma; Travel / Accommodation / Expenses: Sanofi; Travel / Accommodation / Expenses: Aventis; Travel / Accommodation / Expenses: Curevac; Travel / Accommodation / Expenses: Ferring. R.Z. Szmulewitz: Advisory / Consultancy: AstraZeneca; Advisory / Consultancy, Research grant / Funding (self): AbbVie; Advisory / Consultancy: Exelixis; Advisory / Consultancy: Merck; Advisory / Consultancy: Amgen; Advisory / Consultancy, Research grant / Funding (self): Janssen Oncology; Advisory / Consultancy: Sanofi; Advisory / Consultancy, Research grant / Funding (self): Astellas Pharma; Advisory / Consultancy: Pfizer; Research grant / Funding (self): Incyte; Research grant / Funding (self): Macrogenics; Travel / Accommodation / Expenses: Concept Therapeutics. D.P. Petrylak: Advisory / Consultancy, Shareholder / Stockholder / Stock options: Bellicum; Shareholder / Stockholder / Stock options: Tyme; Advisory / Consultancy: Astellas Pharma; Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Advisory / Consultancy, Research grant / Funding (institution): Bayer; Research grant / Funding (institution): Genentech; Research grant / Funding (institution): Merck; Advisory / Consultancy: Exelixis; Advisory / Consultancy: Ferring; Advisory / Consultancy, Research grant / Funding (institution): Johnson & Johnson; Speaker Bureau / Expert testimony: Celgene; Advisory / Consultancy, Research grant / Funding (institution): Medivation, Lilly; Advisory / Consultancy, Research grant / Funding (institution): Millineum, Dendreon, Aventis; Research grant / Funding (institution): Progenics; Advisory / Consultancy, Research grant / Funding (institution): Roche Laboratories; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Sanofi; Research grant / Funding (institution): Innocrin; Research grant / Funding (institution): Agensys; Research grant / Funding (institution): Clovis; Research grant / Funding (institution): Endocyte; Advisory / Consultancy, Research grant / Funding (institution): Pfizer. J. Holzbeierlein: Research grant / Funding (self): Astellas Pharma; Research grant / Funding (self): MDX Health. A. Villers: Advisory / Consultancy: Astellas France; Research grant / Funding (institution): Astellas Pharma. A.A. Azad: Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Astellas Pharma; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Novartis; Advisory / Consultancy, Travel / Accommodation / Expenses: Janssen; Advisory / Consultancy: Sanofi; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy, Travel / Accommodation / Expenses: Pfizer; Advisory / Consultancy: Bristol-Myers Squibb; Advisory / Consultancy, Travel / Accommodation / Expenses: Tolmar; Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Amgen; Speaker Bureau / Expert testimony: Bayer; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Novartis. A. Alcaraz: Travel / Accommodation / Expenses: Astellas; Travel / Accommodation / Expenses: Olympus; Travel / Accommodation / Expenses: Ipsen. B.Y. Alekseev: Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Travel / Accommodation / Expenses: AstraZeneca; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Travel / Accommodation / Expenses: Astellas Pharma; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Travel / Accommodation / Expenses: Bayer; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Travel / Accommodation / Expenses: BMS; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Ferring; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Travel / Accommodation / Expenses: Janssen; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Travel / Accommodation / Expenses: MSD; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Travel / Accommodation / Expenses: Pfizer; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Sanofi. T. Iguchi: Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Bayer; Advisory / Consultancy, Speaker Bureau / Expert testimony: Janssen; Speaker Bureau / Expert testimony, Research grant / Funding (institution): Astellas Pharma; Speaker Bureau / Expert testimony: Sanofi; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Bayer. N.D. Shore: Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: Bayer; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: Janssen Scientific Affairs; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: Dendreon; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Tolmar; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Ferring; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Medivation/Astellas; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Amgen; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Pfizer; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: AstraZeneca; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Genentech/Roche; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Myovant Sciences; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: Bayer. B. Rosbrook: Shareholder / Stockholder / Stock options, Full / Part-time employment: Pfizer Inc. B. Baron: Advisory / Consultancy, Full / Part-time employment: Astellas. G.P. Haas: Full / Part-time employment: Astellas Pharma. R. Morlock: Advisory / Consultancy: Abbott Medical Optics; Advisory / Consultancy: Ironwood; Advisory / Consultancy: Genentech; Full / Part-time employment: Astellas Pharma. K. Ramaswamy: Shareholder / Stockholder / Stock options, Full / Part-time employment: Pfizer Inc. A.J. Armstrong: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Sanofi; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: Dendreon; Honoraria (institution): Janssen Oncology; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: Bayer; Advisory / Consultancy, Research grant / Funding (institution): Novartis; Advisory / Consultancy, Research grant / Funding (institution): Medivation; Advisory / Consultancy, Travel / Accommodation / Expenses: Janssen Biotech; Advisory / Consultancy, Research grant / Funding (institution): Pfizer; Advisory / Consultancy, Travel / Accommodation / Expenses: Astellas Scientific & Medical Affairs Inc; Research grant / Funding (institution): Gilead Sciences; Research grant / Funding (institution): Roche/Genentech; Research grant / Funding (institution): Active Biotech; Research grant / Funding (institution): Bristol-Myers Squibb; Research grant / Funding (institution): Astellas Pharma; Research grant / Funding (institution): Janssen.