Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Clinical Trial
. 2022 Mar 10;40(8):837-846.
doi: 10.1200/JCO.21.00941. Epub 2021 Dec 20.

Health-Related Quality of Life in Metastatic, Hormone-Sensitive Prostate Cancer: ENZAMET (ANZUP 1304), an International, Randomized Phase III Trial Led by ANZUP

Martin R Stockler  1 , Andrew J Martin  1 , Ian D Davis  2 , Haryana M Dhillon  3 , Stephen D Begbie  4 , Kim N Chi  5 , Simon Chowdhury  6 , Xanthi Coskinas  1 , Mark Frydenberg  2 , Wendy E Hague  1 , Lisa G Horvath  7 , Anthony M Joshua  8 , Nicola J Lawrence  9 , Gavin M Marx  10 , John McCaffrey  11 , Ray McDermott  12 , Margaret McJannett  13 , Scott A North  14 , Francis Parnis  15 , Wendy R Parulekar  16 , David W Pook  17 , M Neil Reaume  18 , Shahneen Sandhu  19 , Alvin Tan  20 , Thean Hsiang Tan  21 , Alastair Thomson  22 , Francisco Vera-Badillo  23 , Scott G Williams  19 , Diana G Winter  1 , Sonia Yip  1 , Alison Y Zhang  1 , Robert R Zielinski  24 , Christopher J Sweeney  25 ; ENZAMET Trial Investigators and the Australian and New Zealand Urogenital and Prostate Cancer Trials Group (ANZUP)
Affiliations
Clinical Trial

Health-Related Quality of Life in Metastatic, Hormone-Sensitive Prostate Cancer: ENZAMET (ANZUP 1304), an International, Randomized Phase III Trial Led by ANZUP

Martin R Stockler et al. J Clin Oncol. .

Abstract

Purpose: We previously reported that enzalutamide improved overall survival when added to standard of care in metastatic, hormone-sensitive prostate cancer. Here, we report its effects on aspects of health-related quality of life (HRQL).

Methods: HRQL was assessed with the European Organisation for Research and Treatment of Cancer core quality-of-life questionnaire and QLM-PR25 at weeks 0, 4, 12, and then every 12 weeks until progression. Scores from week 4 to 156 were analyzed with repeated measures modeling to calculate group means and differences. Deterioration-free survival was from random assignment until the earliest of death, clinical progression, discontinuation of study treatment, or a worsening of 10 points or more from baseline in fatigue, physical function, cognitive function, or overall health and quality of life (OHQL). HRQL scores range from 0 (lowest possible) to 100 (highest possible).

Results: HRQL was assessed in 1,042 of 1,125 participants (93%). Differences in means favored control over enzalutamide for fatigue (5.2, 95% CI, 3.6 to 6.9; P < .001), cognitive function (4.0, 95% CI, 2.5 to 5.5; P < .001), and physical function (2.6, 95% CI, 1.3 to 3.9; P < .001), but not OHQL (1.2, 95% CI, -0.2 to 2.7; P = .1). Deterioration-free survival rates at 3 years, and log-rank P values comparing the whole distributions, favored enzalutamide over control for OHQL (31% v 17%; P < .0001), cognitive function (31% v 20%; P = .001), and physical function (31% v 22%; P < .001), but not fatigue (24% v 18%; P = .16). The effects of enzalutamide on HRQL were independent of baseline characteristics.

Conclusion: Enzalutamide was associated with worsening of self-reported fatigue, cognitive function, and physical function, but not OHQL. Enzalutamide was associated with improved deterioration-free survival for OHQL, physical function, and cognitive function because delays in disease progression outweighed early deteriorations in these aspects of HRQL.

Trial registration: ClinicalTrials.gov NCT02446405.

PubMed Disclaimer

Conflict of interest statement

Martin R. StocklerSpeakers' Bureau: Astellas PharmaResearch Funding: Astellas, Celgene, Bayer, Bionomics, Medivation, Sanofi, Pfizer, AstraZeneca, Bristol Myers Squibb, Roche, Amgen, Merck Sharp & Dohme, Tilray, BeiGeneExpert Testimony: Medivation/Pfizer Ian D. DavisResearch Funding: Astellas Pharma, Pfizer, Roche/Genentech, MSD Oncology, AstraZeneca, Janssen Oncology, Eisai, Bayer, Amgen, Bristol Myers Squibb, Movember Foundation, Exelixis, Ipsen, Medivation, SeagenPatents, Royalties, Other Intellectual Property: International Patent Application No: PCT/US2004/032147 (NY-ESO-1) through Ludwig Institute for Cancer Research Haryana M. DhillonHonoraria: Janssen Oncology Stephen D. BegbieHonoraria: Janssen OncologyConsulting or Advisory Role: Astellas Pharma, MSD Oncology, Merck SeronoSpeakers' Bureau: Astellas MedivationResearch Funding: Merck Serono, Janssen Oncology, Boston Biomedical, Pfizer/EMD Serono, Bristol Myers Squibb Kim N. ChiStock and Other Ownership Interests: JanssenHonoraria: Astellas Pharma, Bayer, AstraZeneca, Roche, Merck, ESSAConsulting or Advisory Role: Astellas Pharma, Janssen, Sanofi, Amgen, Bayer, AstraZeneca, Roche, POINT Biopharma, Daiichi Sankyo, Merck, Constellation PharmaceuticalsSpeakers' Bureau: JanssenResearch Funding: Astellas Pharma, Bayer, Sanofi, Bristol Myers Squibb, Merck, Roche, AstraZeneca, Novartis, Pfizer, ESSAPatents, Royalties, Other Intellectual Property: AstraZenecaExpert Testimony: Novartis Simon ChowdhuryStock and Other Ownership Interests: Clovis OncologyHonoraria: Novartis, Clovis OncologyConsulting or Advisory Role: Astellas Pharma, Bayer, Pfizer, Janssen-Cilag, BeiGene, NovartisSpeakers' Bureau: Janssen-Cilag, Sanofi/Aventis Mark FrydenbergEmployment: Genesis Cancer Care, Telix Pharmaceuticals Lisa G. HorvathEmployment: Connected Medical SolutionsLeadership: Connected Medical SolutionsStock and Other Ownership Interests: Imagion BiosystemsHonoraria: Imagion BiosystemsSpeakers' Bureau: Astellas PharmaExpert Testimony: Astellas PharmaTravel, Accommodations, Expenses: Janssen-Cilag, Pfizer Anthony M. JoshuaStock and Other Ownership Interests: Pricilium TherapeuticsConsulting or Advisory Role: Neoleukin Therapeutics, Janssen Oncology, Ipsen, AstraZeneca, Sanofi, Noxopharm, IQvia, Pfizer, Novartis, Bristol Myers Squibb, Merck Serono, EisaiResearch Funding: Bristol Myers Squibb, Janssen Oncology, Merck Sharp & Dohme, Mayne Pharma, Roche/Genentech, Bayer, Macrogenics, Lilly, Pfizer, AstraZeneca, Corvus Pharmaceuticals, Lilly Gavin M. MarxStock and Other Ownership Interests: JanssenHonoraria: RocheConsulting or Advisory Role: Janssen Ray McDermottStock and Other Ownership Interests: BayerHonoraria: Sanofi, Janssen, Astellas Pharma, Bristol Myers Squibb, Merck Sharp & Dohme, Pfizer, Novartis, Clovis OncologyConsulting or Advisory Role: MSD OncologyResearch Funding: Janssen, Bayer, Astellas PharmaExpert Testimony: PfizerTravel, Accommodations, Expenses: Janssen-Cilag, Roche, Ipsen Scott A. NorthStock and Other Ownership Interests: Janssen-OrthoHonoraria: Astellas Pharma, Pfizer, Sanofi, Merck, Roche Canada, BMSConsulting or Advisory Role: Sanofi, Pfizer, Roche Canada, Merck, AstraZeneca, Janssen, Bristol Myers Squibb, EMD SeronoSpeakers' Bureau: Astellas PharmaResearch Funding: Janssen, AstraZenecaExpert Testimony: AstraZenecaTravel, Accommodations, Expenses: Astellas Pharma Francis ParnisHonoraria: Janssen OncologyConsulting or Advisory Role: Ipsen, Merck Serono M. Neil ReaumeStock and Other Ownership Interests: NovartisHonoraria: Ipsen, AstraZeneca, Pfizer, EMD SeronoSpeakers' Bureau: AstraZeneca Shahneen SandhuStock and Other Ownership Interests: Bristol Myers SquibbHonoraria: Merck, Merck Serono, AstraZenecaConsulting or Advisory Role: Merck Sharp & Dohme, Bristol Myers Squibb/Roche, Bristol Myers SquibbSpeakers' Bureau: Merck, Roche/Genentech, AmgenResearch Funding: AstraZeneca, Merck, Endocyte/Advanced Accelerator Applications, Genentech/Roche, Novartis Thean Hsiang TanSpeakers' Bureau: Janssen Oncology Alastair ThomsonConsulting or Advisory Role: Novartis, RocheSpeakers' Bureau: Genomic Health, Novartis, LillyTravel, Accommodations, Expenses: Ipsen, BMS, Astellas Pharma, EUSA Pharma Francisco Vera-BadilloHonoraria: BayerConsulting or Advisory Role: AstraZeneca, Janssen OncologySpeakers' Bureau: AstraZeneca/MedImmune Scott G. WilliamsHonoraria: AmgenConsulting or Advisory Role: JanssenExpert Testimony: Astellas Pharma Alison Y. ZhangStock and Other Ownership Interests: Astellas PharmaHonoraria: Mundipharma, AstraZeneca, Pfizer, Bayer, MSD Oncology, Merck Sharp & DohmeConsulting or Advisory Role: Janssen Oncology, Pfizer, Merck Robert R. ZielinskiStock and Other Ownership Interests: BMSHonoraria: Pfizer, Roche/GenentechConsulting or Advisory Role: MSD OncologySpeakers' Bureau: BMSiResearch Funding: AstraZeneca Christopher J. SweeneyStock and Other Ownership Interests: LeuchemixConsulting or Advisory Role: Sanofi, Janssen Biotech, Astellas Pharma, Bayer, Genentech/Roche, AstraZeneca, Pfizer, Amgen, LillyResearch Funding: Janssen Biotech, Astellas Pharma, Sanofi, Bayer, Dendreon, PfizerPatents, Royalties, Other Intellectual Property: Leuchemix, Parthenolide, Dimethylaminoparthenolide; Exelixis: Abiraterone plus cabozantinib combinationNo other potential conflicts of interest were reported.

Figures

FIG 1.
FIG 1.
Health-related quality of life scores over time by randomly assigned treatment for (A) the EORTC core quality-of-life questionnaire and (B) EORTC QLM-PR25. *P < .05, **P < .01, ***P < .001. ADT, androgen deprivation therapy; EORTC, European Organisation for Research and Treatment of Cancer; EORTC QLM-PR25, European Organisation for Research and Treatment of Cancer disease-specific module for prostate cancer; OHQL, overall health and quality of life.
FIG 2.
FIG 2.
Early deteriorations in health-related quality of life (A) by randomly assigned treatment for the whole group and (B) by physician-assigned plan for early chemotherapy with docetaxel. OHQL, overall health and quality of life.
FIG 3.
FIG 3.
Kaplan-Meier curves for deterioration-free survival by randomly assigned treatment: (A) physical functioning, (B) OHQL, (C) cognitive functioning, and (D) fatigue. OHQL, overall health and quality of life.
See this image and copyright information in PMC

Comment in

References

    1. Scher HI, Fizazi K, Saad F, et al. ; Increased survival with enzalutamide in prostate cancer after chemotherapy. N Engl J Med 367:1187-1197, 2012 - PubMed
    1. Beer TM, Armstrong AJ, Rathkopf D, et al. : Enzalutamide in men with chemotherapy-naïve metastatic castration-resistant prostate cancer: Extended analysis of the phase 3 PREVAIL study. Eur Urol 71:151-154, 2017 - PMC - PubMed
    1. Davis ID, Martin AJ, Stockler MR, et al. : ENZAMET trial investigators and the Australian and New Zealand urogenital and prostate cancer trials group. Enzalutamide with standard first-line therapy in metastatic prostate cancer. N Engl J Med 381:121-131, 2019 - PubMed
    1. Sweeney CJ, Chen YH, Carducci M, et al. : Chemohormonal therapy in metastatic hormone-sensitive prostate cancer. N Engl J Med 373:737-746, 2015 - PMC - PubMed
    1. Piccirillo JF, Tierney RM, Costas I, et al. : Prognostic importance of comorbidity in a hospital-based cancer registry. JAMA 291:2441-2447, 2004 - PubMed

Publication types

MeSH terms

Associated data