@article{94d4f78cf55441c089edeb69141c99c0,
title = "Overall Survival of Men with Metachronous Metastatic Hormone-sensitive Prostate Cancer Treated with Enzalutamide and Androgen Deprivation Therapy",
abstract = "Men who initially present with localized prostate cancer and later develop metachronous metastases have a better prognosis than men with de novo metastatic disease and often have a low burden of disease on conventional imaging. Some have disease amenable to metastasis-directed therapy for lymph node or bone metastases, a strategy used by some because no documented overall survival (OS) benefit of combination systemic therapy in this setting. We report data for patients prospectively classified as “M0” at initial diagnosis from the interim analysis of the ENZAMET trial, with 34 mo of median follow-up for survivors. A total of 312 (28%) of the 1125 enrolled patients were classified as M0 at diagnosis, and 205 (66%) of the 312 patients had low-volume disease at study entry as per the CHAARTED criteria. The hazard ratio for OS, that is, HR(OS), was 0.56 (95% confidence interval [CI]: 0.29–1.06) with the addition of enzalutamide for all patients with metachronous metastatic hormone-sensitive prostate cancer, and for the low-volume subset the HR(OS) was 0.40 (95% CI: 0.16–0.97). The 3-yr OS was 83% without and 89% with enzalutamide for all patients with metachronous metastases, and 83% and 92%, respectively, for the low-volume subset. Intensification of hormonal therapy should strongly be considered for these men. Patient summary: Many men present with prostate cancer that has spread to distant sites beyond the prostate gland years after their initial diagnosis and treatment, while others have distant spread at the time the cancer is diagnosed. On average, men whose cancer comes back years after the initial diagnosis often survive much longer than men whose cancer has been found to spread to distant sites when it is first diagnosed. In this report, we demonstrate strong evidence for the first time that the survival of men whose cancer comes back years later is improved when drugs such as enzalutamide or apalutamide are added to testosterone suppression in this setting.",
keywords = "Enzalutamide, Low volume, Metachronous, Metastatic hormone-sensitive prostate cancer",
author = "Sweeney, {Christopher J.} and Martin, {Andrew J.} and Stockler, {Martin R.} and Stephen Begbie and Chi, {Kim N.} and Simon Chowdhury and Xanthi Coskinas and Mark Frydenberg and Hague, {Wendy E.} and Horvath, {Lisa G.} and Joshua, {Anthony M.} and Lawrence, {Nicola J.} and Marx, {Gavin M.} and John McCaffrey and Ray McDermott and Margaret McJannett and North, {Scott A.} and Francis Parnis and Wendy Parulekar and Pook, {David W.} and Reaume, {M. Neil} and Sandhu, {Shahneen K.} and Alvin Tan and Tan, {Thean Hsiang} and Alastair Thomson and Emily Tu and Francisco Vera-Badillo and Williams, {Scott G.} and Sonia Yip and Zhang, {Alison Y.} and Zielinski, {Robert R.} and Davis, {Ian D.} and {for the ENZAMET Trial Investigators and the Australian and New Zealand Urogenital and Prostate Cancer Trials Group (ANZUP)}",
note = "Funding Information: Financial disclosures: Christopher J. Sweeney certifies that all conflicts of interest, including specific financial interests and relationships and affiliations relevant to the subject matter or materials discussed in the manuscript (eg, employment/affiliation, grants or funding, consultancies, honoraria, stock ownership or options, expert testimony, royalties, or patents filed, received, or pending), are the following: Stephen Begbie—reports grants and personal fees from Astellas, Janssen, Pfizer, and MSD; personal fees from Merck Serono and Amgen. Kim Chi—reports grants and personal fees from Astellas, during the conduct of the study; grants and personal fees from AstraZeneca, Bayer, Astellas, Novartis, Pfizer, Point Biopharma, Roche, and Sanofi; personal fees from Daiichi Sankyo, Merck, and Bristol-Myers Squibb, outside the submitted work. Simon Chowdhury—reports personal fees and nonfinancial support from Johnson & Johnson, Astellas, and Sanofi; personal fees from Clovis, outside the submitted work. Xanthi Coskina—reports grants from Astellas during the conduct of the study. Ian Davis—reports grants from National Health and Medical Research Council, during the conduct of the study; other from ANZUP Cancer Trials Group, Movember Foundation, Pfizer, Eisai, ANZUP Cancer Trials Group, Bayer, AstraZeneca, Roche, Astellas, Janssen, Bristol-Myers Squibb, Ipsen, Merck, and Tokai, outside the submitted work; in addition, Dr. Davis has a patent, In vivo efficacy of NY-ESO-1 plus adjuvant (PCT/US2004/032147) with royalties paid to Ludwig Institute For Cancer Research, and he is the Director and a chair of ANZUP Cancer Trials Group, the sponsor of the ENZAMET trial (unremunerated); all honoraria for work with industry are invoiced by and paid directly to ANZUP Cancer Trials Group, with no pass-through payments of any sort. Mark Frydenberg and Wendy Hague—have nothing to disclose. Lisa Horvath—reports grants and nonfinancial support from Astellas outside the submitted work. Anthony Joshua—has received grants and personal fees from Bristol-Myers Squibb, Janssen Oncology, and Pfizer; grants from Merck Sharp & Dohme, Mayne Pharma, Roche/Genetech, Bayer, Macrogenics, and Lilly; personal fees from Neolukin, Ipsen, AstraZeneca, Sanofi, Noxopharm, IOvia, Novartis, and Merck Serono, outside the submitted work. Nicola Lawrence—reports grants and personal fees from Merck Sharpe & Dohme. Andrew Martin—reports grants from Astellas during the conduct of the study. Gavin Marx and John McCaffrey—have nothing to disclose. Ray McDermott—reports grants and personal fees from Clovis and Bayer; personal fees and nonfinancial support from Pfizer and Janssen; grants from Amgen, Bristol Myers Squibb, Merck; nonfinancial support from Celgene, outside the submitted work. Margaret McJannett—reports grants from Astellas during the conduct of the study. Scott North, Francis Parnis, and Wendy Parulekar—have nothing to disclose. David Pook—reports other from ANZUP during the conduct of the study; nonfinancial support from Astellas; other from Medivation, Pfizer, Roche, Bayer, BMS, MSD, and Ipsen, outside the submitted work. Martin Neil Reaume—reports personal fees from Merck, Novartis, Roche, and Ipsen; grants and personal fees from AstraZeneca; personal fees from Eisai, Pfizer, and Astellas, outside the submitted work. Shahneen Sandhu—reports grants from Novartis/AAA, AstraZeneca, Merck Sharp and Dohme, and Genetech; personal fees from AstraZeneca, Merck Sharp and Dohme, Bristol Myer Squibb, and AstraZeneca, outside the submitted work. Martin Stockler—reports grants from Astellas, during the conduct of the study; grants from Astellas, Amgen, AstraZeneca, Bayer, Bionomics, Bristol-Myers Squibb, Celgene, Medivation, Merck Sharp & Dohme, Pfizer, Roche, Sanofi, Specialised Therapeutics, and Tilray, outside the submitted work. Christopher Sweeney—reports personal fees from Amgen, Genentech/Roche, and Lilly; grants and personal fees from Astellas, Bayer, Pfizer, Sanofi; grants from Dendreon; other from Leuchemix, outside the submitted work; in addition, Dr. Sweeney reports a patent, Use of parthenolide to inhibit cancer (6,890,946) issued, and a patent, Drug combinations to treat cancer (WO2014165779 A1) licensed to Exelixis. Alvin Tan and Thean Hsiang Tan—have nothing to disclose. Alastair Thomson—reports nonfinancial support from Astellas outside the submitted work. Emily Tu—reports grants from Astellas during the conduct of the study. Francisco Vera-Badillo and Scott Williams—have nothing to disclose. Sonia Yip—reports grants from Astellas during the conduct of the study. Alison Zhang—reports grants and nonfinancial support from Astellas; grants and personal fees from AstraZeneca, Merck Sharpe & Dohme, and Janssen; grants from Pfizer and Merck, outside the submitted work. Robert R. Zielinski—reports personal fees and nonfinancial support from Bristol-Myers Squibb; personal fees from Merck Sharpe & Dohme, Pfizer, AstraZeneca, and Tilray, outside the submitted work. Funding Information: Acknowledgments: We acknowledge the ANZUP Board, Scientific Advisory Committee, Prostate Cancer Subcommittee, Consumer Advisory Panel, and Independent Data Safety and Monitoring Committee, NHMRC Clinical Trials Centre, Canadian Cancer Trials Group, and Cancer Trials Ireland, and Majid Tabesh and P{\'a}draig Moran. We also acknowledge and thank Astellas for provision of financial support and enzalutamide. Funding Information: Funding/Support and role of the sponsor: This work was supported by Astellas Scientific and Medical Affairs, a grant ( 704970 ) from the Canadian Cancer Society (to Canadian Cancer Trials Group), the Support for Cancer Clinical Trials Program of Cancer Australia, and an NHMRC practitioner fellowship ( APP1102604 ; to Ian D. Davis) and program grants ( 1037786 and 1150467 ; to NHMRC Clinical Trials Centre) from the National Health and Medical Research Council of the Australian Government Department of Health . ANZUP receives infrastructure funding from the Australian Government through Cancer Australia . Publisher Copyright: {\textcopyright} 2021 European Association of Urology Copyright: Copyright 2021 Elsevier B.V., All rights reserved.",
year = "2021",
month = sep,
doi = "10.1016/j.eururo.2021.05.016",
language = "English",
volume = "80",
pages = "275--279",
journal = "European Urology",
issn = "0302-2838",
publisher = "Elsevier BV",
number = "3",
}
