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Overall survival in patients with metastatic hormone-sensitive prostate cancer (mHSPC) treated with enzalutamide + androgen deprivation therapy by high or low disease volume and progression to mHSPC (M0 at diagnosis) or de novo mHSPC (M1 at diagnosis): post hoc analysis of the phase 3 ARCHES trial
Andrew J. Armstrong, MD, MSc1, Taro Iguchi, MD, PhD2, Arun A. Azad, MBBS, PhD3, Russell Z. Szmulewitz, MD4, Jeffrey Holzbeierlein, MD5, Arnauld Villers, MD, PhD6, Antonio Alcaraz, MD, PhD7, Boris Alekseev, MD8, Neal D. Shore, MD9, Francisco Gomez-Veiga, MD, PhD10, Brad Rosbrook, MS11, Fabian Zohren, MD, PhD12, Shunsuke Yamada, MEng13, Gabriel P. Haas, MD14, Arnulf Stenzl, MD15.
1Duke Cancer Institute, Center for Prostate & Urologic Cancers, Durham, NC, USA, 2Department of Urology, Kanazawa Medical University, Ishikawa, Japan, 3Peter MacCallum Cancer Centre, Melbourne, Australia, 4The University of Chicago, Chicago, IL, USA, 5The University of Kansas Medical Center, Kansas City, KS, USA, 6Department of Urology, University Hospital Centre, Lille University, Lille, France, 7Department of Urology, Hospital Clinic de Barcelona, Barcelona, Spain, 8Department of Oncology, Hertzen Moscow Cancer Research Institute, Moscow, Russian Federation, 9Carolina Urologic Research Center, Myrtle Beach, SC, USA, 10Complexo Hospitalario Universitario de A Coruña, Coruña, Spain, 11Pfizer Inc., San Diego, CA, USA, 12Pfizer Inc., New York, NY, USA, 13Data Science, Astellas Pharma Inc, Northbrook, IL, USA, 14Astellas Pharma, Northbrook, IL, USA, 15Department of Urology, University Hospital, Eberhard Karls University of Tübingen, Tübingen, Germany.

BACKGROUND: In ARCHES (NCT02677896), enzalutamide (ENZA) + androgen deprivation therapy (ADT) improved radiographic progression-free survival, overall survival (OS), and other key secondary endpoints vs. placebo (PBO) + ADT for patients with mHSPC (also known as metastatic castration-sensitive prostate cancer). Final OS results confirmed a long-term survival benefit with ENZA + ADT (hazard ratio [HR] 0.66; 95% confidence interval [CI] 0.53, 0.81; p<0.0001). We present post hoc analyses of OS by disease volume and progression to M1 HSPC after initial diagnosis with localized disease (M0) or presentation of de novo mHSPC at initial diagnosis (M1).
METHODS: Patients with mHSPC (N=1150) were randomized 1:1 to ENZA (160 mg/day) + ADT (n=574) or PBO + ADT (n=576), stratified by disease volume and prior docetaxel use. After unblinding, 180 (31.3%) PBO + ADT-treated patients crossed over to open-label ENZA + ADT. High disease volume was defined per CHAARTED criteria. Medical profiles of patients assessed as MX/unknown metastasis at initial diagnosis (n=213) were further reviewed centrally and adjudicated as having either M0 or M1 disease. Median OS and HRs were estimated by Kaplan-Meier methods and Cox proportional hazards, respectively.
RESULTS: Median treatment duration was 40.2 months (mo) for ENZA + ADT and 13.8 mo for PBO + ADT. Inclusive of crossover, 401 (69.6%) PBO + ADT patients had subsequent life-prolonging therapy. OS benefits with ENZA + ADT were seen in all disease volume and M0/M1 populations at a similar magnitude to the overall population (Table). Median OS was not reached in most populations except PBO + ADT patients with high disease volume (45.9 mo; 95% CI 40.1, not estimable [NE]) or high disease volume and M1 disease (43.4 mo; 95% CI 36.4, 49.7) and ENZA + ADT patients with high disease volume and M0 disease (54.2 mo; 95% CI 54.2, NE). Due to the post hoc nature of the analysis, results should be interpreted with caution.
CONCLUSIONS: Our post hoc analysis demonstrates consistent long-term survival benefit with ENZA + ADT vs. PBO + ADT across patients with mHSPC with high and low disease volumes and M0 or M1 disease at initial diagnosis, despite substantial treatment crossover and subsequent therapy use in PBO + ADT patients.


PopulationENZA + ADTa
E/n (%)
E/n (%)
(95% CI)
Overall154/574 (26.8)202/576 (35.1)0.66
(0.53, 0.81)
Low disease volume35/220 (15.9)46/203 (22.7)0.66
(0.43, 1.03)
High disease volume119/354 (33.6)156/373 (41.8)0.66
(0.52, 0.83)
M1127/448 (28.3)170/442 (38.5)0.63
(0.50, 0.79)
M024/117 (20.5)31/129 (24.0)0.71
(0.41, 1.21)
Low disease volume + M126/151 (17.2)34/133 (25.6)0.65
(0.39, 1.08)
Low disease volume + M08/63
12/67 (17.9)0.63
(0.26, 1.54)
High disease volume + M1101/297 (34.0)136/309 (44.0)0.63
(0.48, 0.81)
High disease volume + M016/54
19/62 (30.6)0.77
(0.39, 1.50)

aAs randomized; bHR <1 favors ENZA + ADT; HR >1 favors PBO + ADT.

This study was sponsored by Pfizer and Astellas Pharma, the co-developers of enzalutamide
Prior presentation / copyright permissions: © 2022 American Society of Clinical Oncology, Inc. Reused with permission. This abstract was accepted and previously presented at the 2022 ASCO Genitourinary Cancers Symposium. All rights reserved.
Acknowledgments: Medical writing and editorial support funded by the sponsors were provided by Jake Stoddart, MRes, and Jane Beck, MA, from Complete HealthVizion.

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