Enzalutamide with standard first-line therapy for metastatic hormone-sensitive prostate cancer: a plain language summary of the ENZAMET trial (ANZUP 1304)

Plain Language SummaryWhat is this summary about?ENZAMET is a large international clinical trial involving people with metastatic hormone sensitive prostate cancer (mHSPC). Prior to the trial, standard treatment included testosterone suppression and sometimes, chemotherapy. However, the researchers thought enzalutamide, an anti-androgen (hormone) medicine, which helps to block the effects of testosterone, might be helpful if added to testosterone suppression.What are the key takeaways?ENZAMET showed that the addition of enzalutamide to standard testosterone suppression treatment for mHSPC improved survival, resulting in an increase in the percent of participants alive at 5 years from 57% to 67%. Enzalutamide extended the time until the cancer grew. Side effects were in keeping with what was already known about enzalutamide and these risks were outweighed by improved cancer control in the long-term.What are the main conclusions reported by the researchers?The combination of testosterone suppression plus enzalutamide is a very effective first-line treatment for mHSPC.This is an abstract of the Plain Language Summary of Publication article.View the full Plain Language Summary PDF of this article to read the full-textThis article is related to: AcknowledgmentsAustralian and New Zealand Urogenital and Prostate Cancer Trials Group (ANZUP); National Health and Medical Research Council Clinical Trials Centre, University of Sydney; Cancer Trials Ireland; the Canadian Cancer Trials Group; The Dana Farber Cancer Institute.We thank the trial participants, principal investigators, co-investigators, and study coordinators at all participating centres for their commitment to this trial.Disclosure statementThe authors of this PLSP include; consumers and consumer-members from the ANZUP consumer advisory panel, as well as several original authors from the ENZAMET publication(s). Ciara Conduit – reports honoraria from Astra Zeneca, Bristol-Myers Squibb and Janssen; travel/conference support from Merck and Bayer.Andrisha-Jade Inderjeeth – Speaker fee honoraria from; BMS, Pfizer and Astellas. Eibhlin Mulroe – works for Cancer Trials Ireland. Robert R. Zielinski – Honoraria from Astra Zeneca and Pfizer, and Speaker fees from Pierre Fabre and Janssen. Alastair Thomson – Speaker fees: Novartis (Jan 24), Roche, Exact Sciences (Mar 24), Gilead(Sep 24), Accord (Sep 24), Pfizer (Sep 24), Advisory Boards: MSD, Exact Sciences, Novartis (Oct 23), Amgen, Seagen (Nov 23), Gilead (Dec 23), Support for attending conferences: BMS, MSD, Astellas, Ipsen, EUSA, Lilly, Gilead (Dec 23), Novartis (Oct 23), Menarini Stemline Oncology (Sep 24) and Educational meetings support: Roche Thean Hsiang Tan – Honoraria from Astra Zeneca. Shahneen K. Sandhu – reports institutional research grants or contracts from Novartis, AstraZeneca, Merck Sharp & Dohme, Roche/Genentech, Pfizer, Senhwa Biosciences, AMGEN, Merck Healthcare and support for institution from Merck Sharp Dohme, Bristol Myers Squibb,AstraZeneca, Janssen, Novartis, Roche/Genentech, SkylineDx, Abbvie for participation in advisory boards or consulting. M. Neil Reaume – Advisory Board fees from Pfizer, Ipsen, EMD serono, Merck and Bayer. David W. Pook – Institution grants from Medivation, Bristol-Myers Squibb, SymVivo, Roche, Amgen, Exelixis, Pfizer, Bayer,Astellas Pharma and Merck Sharp & Dohme, Consulting fees from Pfizer & Merck Sharp & Dohme (Institution), and personal: Bristol-Myers Squibb, Pfizer, Merck Sharp & Dohme, Merck, Merck/Pfizer, Bristol Myers Squibb Foundation, Cipla and Astellas Pharma, honoraria from Merck/Pfizer and Bayer, support for attending meetings from Bristol-Myers Squibb, Astellas Pharma, Pfizer, Amgen, Merck/Pfizer and Janssen. Scott A. North – reports honoraria from AAA, Astellas, AstraZeneca,BMS, Eisai, EMD Serono, Ipsen, Janssen, Merck, Pfizer. Anthony Joshua – reports stock ownership Pricilium Therapeutics and Opthea, Consulting or Advisory Role(from his institution): Janssen Oncology, Ipsen, AstraZeneca, Sanofi, Pfizer, Novartis, Merck Serono, IDEAYA Biosciences, IQvia, Bayer, Astellas Pharma, Grey Wolf Therapeutics, Medison, Starpharma, Eisai, Mayne Pharma and MSD Oncology, Patents, Royalties, Other Intellectual Property – Cancer therapeutic methods, Research Funding (through his institution): Bristol-Myers Squibb, Janssen Oncology, Merck Sharp & Dohme, Mayne Pharma, Roche/Genentech, Bayer, Lilly, Pfizer, AstraZeneca,Corvus Pharmaceuticals, Genentech, BeiGene, Myeloid Therapeutics and Immunocore. Lisa Horvath – Honoraria for talks given in 2020, 2022 & 2023 from Astellas Pharma (all honoraria donated to Chirs O'Brien Lifehouse), Support for attending meetings from Astellas Pharma. Ray McDermott - reports honoraria from Janssen,Astellas, BMS, MSD and Ipsen, and travel/conference support from Novartis, Pfizer and Bayer. Simon Chowdhury – Consulting fees from Astellas Pharma, Novartis,Bayer, Pfizer, BeiGene and Janssen-Cilag, Honoraria from Novartis & Clovis Oncology, Speakers bureau from Janssen-Cilag and Sanofi/Aventis and stock from Clovis Oncology. Kim N. Chi – Honoraria/Grants: Astellas, AstraZeneca, Bayer, BMS, Janssen, Merck, Novartis, Pfizer, Point Biopharma and Roche. Alison Y. Zhang – Grants to institution from Astellas, Amgen, Astra Zeneca, Bionomics, Bristol-Myers Squibb, Celgene, Medivation, Merck Sharp & Dohme, Pfizer, Roche, Sanofi and Tilray,Consulting fees from Merck Sharp & Dohme, Honoraria from Merck Sharpe Dohme, Astellas, Bayer, Pfizer, Merck, Mundipharma, Janssen and Astra Zeneca, Advisory Board from Merck, Merck Sharpe Dohme, Astellas and Bayer. Martin R. Stockler – reports Grants to his institution from: Astellas, Amgen, Astra Zeneca, Bionomics,Bristol-Myers Squibb, Celgene, Medivation, Merck Sharp & Dohme, Pfizer, Roche, Sanofi and Tilray. Ian D. Davis – ANZUP Cancer Trials Group, Member of Board of Directors, Director and Chair; unremunerated, Co-Chair of the ENZAMET trial. Christopher J. Sweeney – Consulting or Advisory Role: Janssen, Astellas Pharma,Bayer, Genentech, Pfizer, Lilly, MDS, Point Biopharma; Advancell, CellCentric, Amphista Research Funding: Janssen Biotech (Inst), Astellas Pharma (Inst), Sanofi (Inst),Bayer (Inst), Patents, Royalties, Other Intellectual Property: Parthenolide (Indiana University): dimethylaminoparthenolide (Leuchemix); Exelixis: Abiraterone plus cabozantinib combination; FRAS1 SNP and tristetraprolin and KDM5D as biomarkers of lethal prostate cancer. Stock or Other Ownership: Leuchemix; AdvanCell. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.Patient reviewers on this PLSP have received honorarium from Future Oncology for their review work but have no other relevant financial relationships to disclose.FundingStudy drug and costs of the trial were provided by the manufacturer of enzalutamide (Astellas). The funders had no role in study design, data collection and analysis,decision to publish, or preparation of the manuscript.