Overall Survival of Men with Metachronous Metastatic Hormone-sensitive Prostate Cancer Treated with Enzalutamide and Androgen Deprivation Therapy

doi:10.1016/j.eururo.2021.05.016

. 2021 Sep;80(3):275-279.

doi: 10.1016/j.eururo.2021.05.016. Epub 2021 May 22.

Overall Survival of Men with Metachronous Metastatic Hormone-sensitive Prostate Cancer Treated with Enzalutamide and Androgen Deprivation Therapy

Christopher J Sweeney¹, Andrew J Martin², Martin R Stockler³, Stephen Begbie⁴, Kim N Chi⁵, Simon Chowdhury⁶, Xanthi Coskinas², Mark Frydenberg⁷, Wendy E Hague², Lisa G Horvath⁸, Anthony M Joshua⁹, Nicola J Lawrence¹⁰, Gavin M Marx¹¹, John McCaffrey¹², Ray McDermott¹³, Margaret McJannett¹⁴, Scott A North¹⁵, Francis Parnis¹⁶, Wendy Parulekar¹⁷, David W Pook¹⁸, M Neil Reaume¹⁹, Shahneen K Sandhu²⁰, Alvin Tan²¹, Thean Hsiang Tan²², Alastair Thomson²³, Emily Tu², Francisco Vera-Badillo²⁴, Scott G Williams²⁰, Sonia Yip², Alison Y Zhang²⁵, Robert R Zielinski²⁶, Ian D Davis²⁷; ENZAMET Trial Investigators and the Australian and New Zealand Urogenital and Prostate Cancer Trials Group (ANZUP)

Affiliations

¹ Dana-Farber Cancer Institute, Boston, MA, USA; Harvard Medical School, Boston, MA, USA. Electronic address: christopher_sweeney@dfci.harvard.edu.
² NHMRC Clinical Trials Centre, University of Sydney, Sydney, Australia.
³ NHMRC Clinical Trials Centre, University of Sydney, Sydney, Australia; Concord Cancer Centre, Concord Repatriation General Hospital, Concord, Australia; Chris O'Brien Lifehouse RPA, Sydney, Australia.
⁴ Port Macquarie Base Hospital, Port Macquarie, NSW, Australia; Mid North Coast Cancer Institute Port Macquarie, Port Macquarie, NSW, Australia.
⁵ BC Cancer Agency, Vancouver, BC, Canada; University of British Columbia, Vancouver, BC, Canada.
⁶ Guy's and St Thomas' NHS Foundation Trust Biomedical Research Centre, CRUK and King's College London, UK; Sarah Cannon Research UK, London, UK.
⁷ Monash University, Melbourne, Australia; Australian Urology Associates, Melbourne, Australia.
⁸ Chris O'Brien Lifehouse RPA, Sydney, Australia; University of Sydney, Sydney, Australia.
⁹ Kinghorn Cancer Centre, St Vincents Hospital, Sydney, Australia; Garvan Institute of Medical Research, Sydney, Australia.
¹⁰ Auckland City Hospital, Auckland, New Zealand.
¹¹ University of Sydney, Sydney, Australia; Sydney Adventist Hospital, Wahroonga, Australia.
¹² Cancer Trials Ireland, Dublin, Ireland; Mater Misericordiae University Hospital, Dublin, Ireland.
¹³ Cancer Trials Ireland, Dublin, Ireland; St. Vincent's University Hospital, Dublin, Ireland; University College Dublin, Ireland.
¹⁴ ANZUP Cancer Trials Group, Australia.
¹⁵ Cross Cancer Institute, Edmonton, AB, Canada; University of Alberta, Edmonton, AB, Canada.
¹⁶ Adelaide Cancer Centre, Adelaide, Australia; University of Adelaide, Adelaide, Australia.
¹⁷ Canadian Cancer Trials Group (CCTG) Queen's University, Kingston, ON, Canada.
¹⁸ Monash University, Melbourne, Australia; Monash Health, Melbourne, Australia.
¹⁹ University of Ottawa, Ottawa, ON, Canada; Ottawa Hospital Research Institute, Ottawa, ON, Canada.
²⁰ Peter MacCallum Cancer Centre, Melbourne, Australia; University of Melbourne, Melbourne, Australia.
²¹ Waikato District Health Board, Hamilton, New Zealand.
²² Royal Adelaide Hospital, Adelaide, Australia.
²³ Royal Cornwall Hospital, Truro, Cornwall, UK.
²⁴ Kingston Health Sciences Center, Kingston, ON, Canada; Canadian Cancer Trials Group, Kingston, ON, Canada.
²⁵ NHMRC Clinical Trials Centre, University of Sydney, Sydney, Australia; Chris O'Brien Lifehouse RPA, Sydney, Australia; Macquarie University, Sydney, Australia.
²⁶ Orange Health Service, Central West Cancer Care Centre, Orange, Australia; Western Sydney University, Sydney, Australia.
²⁷ Monash University, Melbourne, Australia; Eastern Health, Melbourne, Australia.

PMID: 34030924
DOI: 10.1016/j.eururo.2021.05.016

Overall Survival of Men with Metachronous Metastatic Hormone-sensitive Prostate Cancer Treated with Enzalutamide and Androgen Deprivation Therapy

Christopher J Sweeney et al. Eur Urol. 2021 Sep.

. 2021 Sep;80(3):275-279.

doi: 10.1016/j.eururo.2021.05.016. Epub 2021 May 22.

Authors

Affiliations

¹ Dana-Farber Cancer Institute, Boston, MA, USA; Harvard Medical School, Boston, MA, USA. Electronic address: christopher_sweeney@dfci.harvard.edu.
² NHMRC Clinical Trials Centre, University of Sydney, Sydney, Australia.
³ NHMRC Clinical Trials Centre, University of Sydney, Sydney, Australia; Concord Cancer Centre, Concord Repatriation General Hospital, Concord, Australia; Chris O'Brien Lifehouse RPA, Sydney, Australia.
⁴ Port Macquarie Base Hospital, Port Macquarie, NSW, Australia; Mid North Coast Cancer Institute Port Macquarie, Port Macquarie, NSW, Australia.
⁵ BC Cancer Agency, Vancouver, BC, Canada; University of British Columbia, Vancouver, BC, Canada.
⁶ Guy's and St Thomas' NHS Foundation Trust Biomedical Research Centre, CRUK and King's College London, UK; Sarah Cannon Research UK, London, UK.
⁷ Monash University, Melbourne, Australia; Australian Urology Associates, Melbourne, Australia.
⁸ Chris O'Brien Lifehouse RPA, Sydney, Australia; University of Sydney, Sydney, Australia.
⁹ Kinghorn Cancer Centre, St Vincents Hospital, Sydney, Australia; Garvan Institute of Medical Research, Sydney, Australia.
¹⁰ Auckland City Hospital, Auckland, New Zealand.
¹¹ University of Sydney, Sydney, Australia; Sydney Adventist Hospital, Wahroonga, Australia.
¹² Cancer Trials Ireland, Dublin, Ireland; Mater Misericordiae University Hospital, Dublin, Ireland.
¹³ Cancer Trials Ireland, Dublin, Ireland; St. Vincent's University Hospital, Dublin, Ireland; University College Dublin, Ireland.
¹⁴ ANZUP Cancer Trials Group, Australia.
¹⁵ Cross Cancer Institute, Edmonton, AB, Canada; University of Alberta, Edmonton, AB, Canada.
¹⁶ Adelaide Cancer Centre, Adelaide, Australia; University of Adelaide, Adelaide, Australia.
¹⁷ Canadian Cancer Trials Group (CCTG) Queen's University, Kingston, ON, Canada.
¹⁸ Monash University, Melbourne, Australia; Monash Health, Melbourne, Australia.
¹⁹ University of Ottawa, Ottawa, ON, Canada; Ottawa Hospital Research Institute, Ottawa, ON, Canada.
²⁰ Peter MacCallum Cancer Centre, Melbourne, Australia; University of Melbourne, Melbourne, Australia.
²¹ Waikato District Health Board, Hamilton, New Zealand.
²² Royal Adelaide Hospital, Adelaide, Australia.
²³ Royal Cornwall Hospital, Truro, Cornwall, UK.
²⁴ Kingston Health Sciences Center, Kingston, ON, Canada; Canadian Cancer Trials Group, Kingston, ON, Canada.
²⁵ NHMRC Clinical Trials Centre, University of Sydney, Sydney, Australia; Chris O'Brien Lifehouse RPA, Sydney, Australia; Macquarie University, Sydney, Australia.
²⁶ Orange Health Service, Central West Cancer Care Centre, Orange, Australia; Western Sydney University, Sydney, Australia.
²⁷ Monash University, Melbourne, Australia; Eastern Health, Melbourne, Australia.

PMID: 34030924
DOI: 10.1016/j.eururo.2021.05.016

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.

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Comment in

Urological Oncology: Prostate Cancer.
Taneja SS. Taneja SS. J Urol. 2021 Dec;206(6):1519-1522. doi: 10.1097/JU.0000000000002226. Epub 2021 Sep 9. J Urol. 2021. PMID: 34496606 No abstract available.

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Overall Survival of Men with Metachronous Metastatic Hormone-sensitive Prostate Cancer Treated with Enzalutamide and Androgen Deprivation Therapy

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Overall Survival of Men with Metachronous Metastatic Hormone-sensitive Prostate Cancer Treated with Enzalutamide and Androgen Deprivation Therapy

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