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

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.

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.

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.

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.

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.