Clinical Outcomes of Enzalutamide in Metastatic Hormone-sensitive Prostate Cancer in Patients Aged <75 and ≥75 Years: ARCHES Post Hoc Analysis.

Autor: Gomez-Veiga F; Complexo Hospitalario Universitario de A Coruña, Coruña, Spain. Electronic address: fgveiga@telefonica.net., Szmulewitz RZ; The University of Chicago, Chicago, IL, USA., Holzbeierlein J; The University of Kansas Medical Center, Kansas City, KS, USA., Azad AA; Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia., Iguchi T; Kanazawa Medical University, Ishikawa, Japan., Villers A; University Hospital Centre, Lille University, Lille, France., Alcaraz A; Hospital Clinic de Barcelona, Barcelona, Spain., Alekseev B; Hertzen Moscow Cancer Research Institute, Moscow, Russia., Shore ND; Carolina Urologic Research Center, Myrtle Beach, SC, USA., Rosbrook B; Pfizer Inc., San Diego, CA, USA., Zohren F; Pfizer Inc., San Diego, CA, USA., Ma J; Astellas Pharma Inc., Northbrook, IL, USA., Haas GP; Astellas Pharma Inc., Northbrook, IL, USA., Stenzl A; University Hospital, Eberhard Karls University of Tübingen, Tübingen, Germany., Armstrong AJ; Duke Cancer Institute Center for Prostate & Urologic Cancers, Duke University, Durham, NC, USA.
Jazyk: angličtina
Zdroj: European urology oncology [Eur Urol Oncol] 2024 Aug; Vol. 7 (4), pp. 860-869. Date of Electronic Publication: 2023 Dec 09.
DOI: 10.1016/j.euo.2023.11.012
Abstrakt: Background: In ARCHES, treatment intensification of androgen deprivation therapy (ADT) with enzalutamide versus placebo improved clinical outcomes in metastatic hormone-sensitive prostate cancer (mHSPC). Understanding the benefits and tolerability of enzalutamide for men aged ≥75 yr may inform disease management.
Objective: To determine whether age is associated with clinical outcomes in mHSPC.
Design, Setting, and Participants: A post hoc analysis of the multinational, double-blind, randomized, placebo-controlled, phase 3 ARCHES trial in 1150 men with mHSPC (median follow-up [mo]: <75 yr, 44.6; ≥75 yr, 44.3) was performed.
Intervention: Randomization 1:1 to enzalutamide (160 mg/d) plus ADT or placebo plus ADT; stratification by disease volume and prior docetaxel use.
Outcome Measurements and Statistical Analysis: Overall survival (OS), radiographic progression-free survival (rPFS), safety, and other secondary endpoints were compared between age groups (<75 and ≥75 yr) and treatment arms (Cox proportional hazard models).
Results and Limitations: Men aged <75 versus ≥75 yr had longer OS (enzalutamide plus ADT: hazard ratio [HR] 0.66; 95% confidence interval [CI] 0.47-0.91; p = 0.02; placebo plus ADT: HR 0.81; 95% CI 0.60-1.09; p = 0.13) and rPFS (enzalutamide plus ADT: HR 0.78; 95% CI 0.58-1.04; p = 0.12; placebo plus ADT: HR 0.98; 95% CI 0.74-1.30; p = 0.007). Enzalutamide improved OS (<75 yr: HR 0.61; 95% CI 0.47-0.79; ≥75 yr: HR 0.76; 95% CI 0.54-1.09) and secondary efficacy endpoints without evidence of statistical heterogeneity, and was generally well tolerated in both age groups, with minimal quality-of-life impact. Older versus younger patients experienced more frequent dose interruptions (20.2% vs 10.9%) and treatment-emergent adverse events (95.2% vs 89.1%). Post hoc examination and small sample size preclude definitive conclusions.
Conclusions: Enzalutamide plus ADT improved efficacy outcomes and was generally well tolerated despite shorter treatment exposure in older patients, indicating enzalutamide's utility in patients with mHSPC aged <75 and ≥75 yr.
Patient Summary: Enzalutamide is a drug approved to treat men with prostate cancer. In this report, we compared patients aged <75 and ≥75 yr treated with enzalutamide plus androgen deprivation therapy to determine whether age affected how long they lived without the cancer spreading to other parts of their body. We found that, although younger patients had more favorable survival outcomes, enzalutamide was associated with longer survival and reduced disease spread in both age groups.
(Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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