Consistent survival benefit of enzalutamide plus androgen deprivation therapy in men with nonmetastatic castration-resistant prostate cancer: PROSPER subgroup analysis by age and region

Abstract

Background: Enzalutamide combined with androgen deprivation therapy (ADT) significantly prolonged metastasis-free survival and overall survival (OS) versus ADT alone in patients with non-metastatic castration-resistant prostate cancer (nmCRPC) with rapidly rising prostate-specific antigen (PSA). The objective of this post hoc analysis of the PROSPER trial is to evaluate OS benefit and safety of enzalutamide in patients across age and regional subgroups.

Patients and methods: Eligible men with nmCRPC, PSA doubling time ≤10 months and PSA ≥2 ng/mL with continued ADT use were randomised 2:1 to enzalutamide 160 mg or placebo. OS and safety were examined by age (<70 vs ≥70 years) and region (North America, Europe, Asia or the rest of the world). The impact of prior and subsequent therapy was also examined.

Results: In total, 1401 men were enrolled (median age, 74 years). Enzalutamide plus ADT reduced the risk of death, independent of age or region. Multivariate analyses identified Eastern Cooperative Oncology Group (ECOG) status (P < 0.0001), log (PSA; P = 0.0002) and subsequent therapy (P < 0.0001) as statistically significant factors impacting OS. Safety was consistent across age and regional subgroups. Any grade treatment-emergent adverse events were similar across age groups, were more common in the placebo group and had regional variation.

Conclusions: In men with nmCRPC and rapidly rising PSA, the benefit and safety of enzalutamide were consistent across age and regional subgroups. Variables impacting OS included ECOG status, log (PSA) and subsequent therapy. CLINICALTRIALS.

Gov identifier: NCT02003924.

Keywords: Antiandrogen therapy; Castration-resistant prostate cancer; Enzalutamide; Prostate cancer; Urological cancers.

Conflict of interest statement

Conflict of interest statement The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Cora N. Sternberg served as a consultant for Janssen-Cilag, Astellas Pharma Inc., Sanofi–Genzyme, Novartis, Bayer, Pfizer Inc., Merck, MSD, AstraZeneca, Immunomedics (now Gilead), Janssen, Foundation Medicine, UroToday and Medscape and has received prior institutional funding from Cougar Biotechnology (now Janssen), Medivation (now Pfizer), Clovis Oncology and Roche-Genentech.Ugo De Giorgi served as a consultant for Janssen, Astellas Pharma Inc., Sanofi, Bayer, Pfizer Inc., BMS, Novartis, Ipsen and Merck. Neal D. Shore served as a consultant for Abbvie, Amgen, Astellas, AstraZeneca, Bayer, BMS, Boston Scientific, Clovis Oncology, Cold Genesys, Dendreon, Exact Imaging, Exact Sciences, FerGene, Foundation Medicine, Genesis Care, Invitae, Janssen, MDxhealth, Merck, Myovant, Myriad, Nymox, Pacific Edge, Pfizer Inc., Phosphorous, Propella, PreView, Sanofi Genzyme, Speciality Networks, Sesen Bio, Tolmar and Urogen. Karim Fizazi served as a consultant for Janssen Oncology, Bayer, Astellas Pharma Inc., Sanofi, Orion Pharma GmbH, Curevac, AstraZeneca, ESSA Pharmaceuticals, Roche/Genentech, Clovis Oncology and Amgen, received money for travel/accommodation expenses from Amgen and has received honoraria from Janssen, Sanofi, Astellas Pharma Inc. and Merck. Bertrand Tombal received personal fees and non-financial support from Amgen, Astellas Pharma Inc., Bayer, Ferring, Janssen and Sanofi; personal fees from Pfizer, Steba Biotech and Takeda and grants from Ferring. David Penson reported no conflict of interest. Fred Saad served as a consultant for Astellas Pharma Inc., Janssen Oncology, Sanofi and AstraZeneca/MedImmune, received honoraria from Astellas Pharma Inc., Janssen Oncology, Sanofi, Bayer and AstraZeneca, received institutional funding from Astellas Pharma Inc., Bayer, Janssen Oncology, Sanofi, Myovant Sciences and AstraZeneca. Eleni Efstathiou received honoraria from Janssen-Cilag, Sanofi and Takeda, served as a consultant for Janssen-Cilag, Sanofi, Astellas Pharma Inc., Bayer, AstraZeneca, Merck Sharp & Dohme, Innocrin Pharma, Takeda and Tolmar, member of the Speakers Bureau for Janssen-Cilag; received research funding from Janssen-Cilag, Sanofi and Astellas Pharma Inc. Katarzyna Madziarska reported no conflict of interest. Joyce Steinberg: employee of Astellas Pharma, Inc. and has an immediate family member with stock ownership in Amgen. Jennifer Sugg: employee of Astellas Pharma, Inc., with stock ownership in AstraZeneca. Xun Lin and Qi Shen: employees and stockholders of Pfizer Inc. Maha Hussain served as a consultant or in an advisory role for AstraZeneca, Bayer, Bristol-Myers Squibb, Daiichi Sankyo Company, Genentech, Janssen and Pfizer Inc., received honoraria and/or travel expenses for educational functions/lectures from Astellas Pharma Inc., AstraZeneca Pharma, Bayer, Genentech/Roche, MLI PeerView, OncLive, Physicians’ Education Resource LLC, Phillips Gilmore Oncology, projects in Knowledge, Research to Practice, Sanofi-Genzyme, UroToday and Precisca, and received institutional research funding from AstraZeneca, Bayer, Genentech, Prostate Cancer Clinical Trials Consortium (PCCTC), Pfizer Inc. and Arvinas.

Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.