Few phase 3 studies have evaluated optimal systemic treatment strategies for patients with oligometastatic hormone-sensitive prostate cancer (HSPC), who may be at risk of undertreatment.
To evaluate outcomes for patients with oligometastatic and polymetastatic HSPC treated with enzalutamide plus androgen deprivation therapy (ADT) versus placebo plus ADT.
This was a post hoc analysis of data for 927 patients with nonvisceral metastatic HSPC in the ARCHES trial (NCT02677896).
Patients were randomized 1:1 to enzalutamide (160 mg/d orally) plus ADT or placebo plus ADT with HSPC categorized as oligometastatic (1-5 metastases) or polymetastatic (≥6 metastases).
The treatment effect on radiographic progression-free survival (rPFS), overall survival (OS), and secondary efficacy endpoints was evaluated in terms of the number of metastases. Safety was assessed. Cox proportional hazards models were used to generate hazard ratios (HRs). The Brookmeyer and Crowley method was used to generate 95% confidence intervals (CIs) for Kaplan-Meier median values.
Enzalutamide plus ADT improved rPFS (HR 0.27, 95% CI 0.16-0.46; p < 0.001), OS (HR 0.59, 95% CI 0.40-0.87; p < 0.005), and secondary endpoints in patients with oligometastatic or polymetastatic disease (rPFS: HR 0.33, 95% CI 0.23-0.46; p < 0.001; OS: HR 0.55, 95% CI 0.41-0.74; p < 0.001). Safety profiles were generally similar across subgroups. Limitations include the small numbers of patients with fewer than three metastases.
This post hoc analysis demonstrated the utility of enzalutamide, irrespective of metastatic burden or type of oligometastatic disease, and suggests that earlier treatment intensification with systemic potent androgen receptor inhibition is advantageous.
This study considered two treatment options for metastatic hormone-sensitive prostate cancer in patients with one to five metastases or six or more metastases. Treatment with enzalutamide plus ADT improved survival and other outcomes over ADT alone, whether patients had few or many metastases.
European urology. 2023 May 11 [Epub ahead of print]
Andrew J Armstrong, Taro Iguchi, Arun A Azad, Arnauld Villers, Boris Alekseev, Daniel P Petrylak, Russell Z Szmulewitz, Antonio Alcaraz, Neal D Shore, Jeffrey Holzbeierlein, Francisco Gomez-Veiga, Brad Rosbrook, Fabian Zohren, Gabriel P Haas, Georgia Gourgiotti, Nader El-Chaar, Arnulf Stenzl
Center for Prostate & Urologic Cancers, Duke Cancer Institute, Durham, NC, USA. Electronic address: ., Kanazawa Medical University, Ishikawa, Japan., Monash Health, Clayton, Victoria, Australia., University Hospital Centre, Lille University, Lille, France., Hertzen Moscow Cancer Research Institute, Moscow, Russia., Department of Medical Oncology, Yale Cancer Center, New Haven, CT, USA., The University of Chicago, Chicago, IL, USA., Hospital Clinic de Barcelona, Barcelona, Spain., Carolina Urologic Research Center, Myrtle Beach, SC, USA., The University of Kansas Medical Center, Kansas City, KS, USA., Hospital Universitario de Salamanca, Instituto de Investigación Biomédica de Salamanca, Salamanca, Spain., Pfizer Inc., San Diego, CA, USA., Astellas Pharma Inc., Northbrook, IL, USA., Department of Biostatistics, Oncology, Astellas Pharma Inc., London, UK., Department of Urology, University Hospital, Eberhard Karls University of Tübingen, Tübingen, Germany.
PubMed http://www.ncbi.nlm.nih.gov/pubmed/37179240