Enough is No Longer Enough

Alicia Morgans | June 27, 2022

The treatment landscape for metastatic hormone-sensitive prostate cancer (mHSPC) has become increasingly complex during the last several years.  Since 2014 we have been aware that combination treatment with androgen deprivation therapy (ADT) and docetaxel chemotherapy is associated with improved overall survival in patients with mHSPC.  Quality of life (QOL) data suggested that better control of the disease with intensified treatment was associated with similar QOL by 12 months after starting chemohormonal treatment.  However, there remained a need to ensure that patients who were not candidates for chemotherapy, or who might not benefit sufficiently from chemotherapy, had an option to improve outcomes.

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Alicia Morgans, MD

Alicia Morgans, MD, MPH Genitourinary Medical Oncologist, Medical Director of Survivorship Program at Dana-Farber Cancer Institute, Boston, Massachusetts. She is a clinician and physician investigator specializing in investigating complications of systemic therapy for prostate cancer survivors. She has expertise in clinical trials and patient-reported outcome measures, and as well as incorporating patient preferences and beliefs into clinical decision making.

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Written by Christopher J.D. Wallis, MD PhD, Rashid Sayyid, MD MSc, & Zachary Klaassen, MD MSc
October 13, 2022

Prostate cancer, while commonly diagnosed early in the disease state, remains the second leading cause of cancer mortality in the United States and Europe1 . Of the 1.3 million new annual diagnoses of prostate cancer, 6% of men have metastases at the time of diagnosis. Such patients are defined as having de novo or synchronous metastatic hormone sensitive prostate cancer (mHSPC).

Written by Zachary Klaassen, MD, MSc, Rashid K. Sayyid, MD, MSc, and Christopher J.D. Wallis, MD, PhD
August 17, 2022

The treatment landscape of metastatic hormone sensitive prostate cancer (mHSPC) has evolved rapidly since the introduction of combination chemohormonal therapy with docetaxel and androgen deprivation therapy (ADT) in 2015.1

 

Written by Christopher J.D. Wallis, MD, PhD, Rashid K. Sayyid, MD, MSc, and Zachary Klaassen, MD, MSc
August 17, 2022
Since 2015, the metastatic hormone sensitive prostate cancer (mHSPC) disease space now has several options of doublet and triplet therapy, using ADT as the backbone of treatment, leading to an overall survival (OS) advantage versus ADT alone. Thus, this has changed the standard of care
Written by Rashid K. Sayyid, MD, MSc, Zachary Klaassen, MD, MSc, and Christopher J.D. Wallis, MD, PhD
August 17, 2022
The treatment landscape of advanced prostate cancer continues to evolve, particularly over the last 5+ years. Although there are several treatment options, including both ADT-based doublet and triplet combinations, available for men with metastatic hormone
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Written by Arun Azad, MBBS PhD FRACP
The treatment of metastatic prostate cancer has seen a paradigm shift, particularly in the management of metastatic hormone sensitive prostate cancer (mHSPC). The developments come not only on the fronts of systemic agents but also in the area of therapy to primary tumour and metastases.
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Conference Highlights Written by Physician-Scientist
Presented by Alice Bernard-Tessier, MD
The 2022 ESMO annual meeting featured a prostate cancer session, including a presentation by Dr. Alice Bernard-Tessier discussing the results of the PEACE-1 trial, specifically the effect of abiraterone-prednisone in mCSPC with neuroendocrine and very high-risk features.
Presented by Rana R. McKay, MD
The 2022 ESMO annual meeting featured a prostate cancer session, including a presentation by Dr. Rana McKay discussing the trial protocol for CYCLONE 3, a phase 3, randomized, double-blind, placebo-controlled study of abemaciclib in combination with abiraterone + prednisone in men with high-risk metastatic hormone sensitive prostate cancer (mHSPC).
Presented by Ursula M. Vogl, MD, MBA
The 2022 EAU annual meeting featured a joint session of the EAU, EANM, ESMO, and ESTRO societies examining modern diagnostic and therapeutic approaches in prostate cancer, including a presentation by Dr. Ursula Vogl discussing the treatment landscape of hormone sensitive recurrent M1 prostate cancer.
Presented by Neal D. Shore, MD, FACS
The 2022 ASCO annual meeting featured a session on prostate cancer, including a trial in progress presentation by Dr. Neal Shore discussing ARASEC, an open-label study of androgen receptor inhibition with darolutamide + ADT versus ADT in men with metastatic hormone-sensitive prostate cancer (mHSPC) using an external control arm.
Presented by Ian Davis MB, BS, PhD, FRACP, FAChPM

The 2022 ASCO annual meeting featured an oral abstract session on prostate cancer, including a presentation by Dr. Ian Davis discussing updated overall survival outcomes in ENZAMET (ANZUP 1304), an international, cooperative group trial of enzalutamide in mHSPC. Dr. Davis started by highlighting several points regarding the current mHSPC clinical knowledge. First, prognostic variables associated with better outcomes with testosterone suppression alone include (i) low volume being better than high volume disease, and (ii) metachronous metastatic presentation is better than synchronous. Second, the OS benefit of combination treatment by prognostic groups:

Presented by Bertrand Tombal, MD, PhD
The 2022 Advanced Prostate Cancer Consensus Conference (APCCC) Hybrid Meeting included a session on the management of metastatic hormone sensitive prostate cancer (mHSPC) and a presentation by Dr. Bertrand Tombal discussing de-escalation strategies in mHSPC. Dr. Tombal started his presentation by highlighting the current landscape of advanced prostate cancer as it stands in 2022:
Presented by Andrew Armstrong, MD
The 2022 Advanced Prostate Cancer Consensus Conference (APCCC) Hybrid Meeting included a session on the management of metastatic hormone sensitive prostate cancer (mHSPC) and a presentation by Dr. Andrew Armstrong discussing the uptake of new treatment options for mHSPC in real life, including education, access, use, and diversity.
Presented by Christopher Sweeney, MBBS
The 2022 Advanced Prostate Cancer Consensus Conference (APCCC) Hybrid Meeting included a session on the management of metastatic hormone sensitive prostate cancer (mHSPC) and a presentation by Dr. Christopher Sweeney discussing treatment intensification strategies in mHSPC, specifically triplet therapies. Dr. Sweeney started by highlighting that there are several life-prolonging treatment options for men with mHSPC.
Presented by Daniel Spratt, MD
In the session of the 2022 Advanced Prostate Cancer Consensus Conference focusing on the treatment of patients with oligometastatic and oligoprogressive prostate cancer, Dr. Spratt discussed the evidence for metastasis directed therapy (MDT) in patients with synchronous and metachronous metastatic hormone sensitive prostate cancer (mHSPC).
Presented by Alicia Morgans, MD, MPH
 The 2022 Advanced Prostate Cancer Consensus Conference (APCCC) Hybrid Meeting included a session on the management of metastatic hormone sensitive prostate cancer (mHSPC) and a presentation by Dr. Alicia Morgans discussing the treatment of vulnerable/frail patients with mHSPC.
Presented by Pedro Barata, MD, MSc
Dr. Barata and colleagues gathered data from patients by 50 participating physicians, each who aggregated information on four patients with mCSPC and four patients with mCRPC, a subset of the latter who had treatment information from their mCSPC disease.
Presented by Joaquin Mateo MD, PhD
Dr. Joaquin Mateo described the rationale and design for the ZZFIRST trial, examining enzalutamide and talazoparib for the treatment of metastatic hormone-naïve prostate cancer (mHNPC).
Presented by A. Oliver Sartor, MD
A. Oliver Sartor presented the rationale and design of the PSMAddition trial. The PSMAddition trial is an international, prospective, open-label, randomized, phase 3 trial in adults with mHSPC.
Presented by Dayanand Sharma, MD, DNB,
Dr. Sharma presented the design of the ARANOTE trial, assessing darolutamide and androgen deprivation therapy (ADT), as compared to ADT alone in patients with metastatic hormone-sensitive prostate cancer (mHSPC).
Presented by Guilhem Roubaud, MD
Dr. Roubaud presented an analysis of bone mineral density in men treated on the PEACE-1 trial. In terms of assessing the toxicity of abiraterone acetate and prednisone, a planned study amendment sought to analyze whether the addition of abiraterone acetate and prednisone was associated with increased bone loss.
Presented by Matthew Raymond Smith, PhD, MD

Darolutamide is a related, but structurally distinct, androgen receptor inhibitor which has demonstrated improved metastasis-free survival and overall survival in patients with nonmetastatic castration-resistant prostate cancer (CRPC). In an oral abstract presentation Dr. Smith presented the first results of the ARASENS trial which examined darolutamide in combination with docetaxel and ADT compared to docetaxel and ADT. 

 

Presented by Matthew R. Smith, MD, PhD
(UroToday.com) In this presentation, Dr. Smith presented results of the ARASENS study. ARASENS is a randomized phase 3 trial of darolutamide versus placebo in combination with docetaxel and androgen-deprivation therapy (ADT) for metastatic hormone-sensitive prostate cancer (mHSPC). Darolutamide is a highly potent androgen receptor (AR) inhibitor with low blood-brain barrier penetration and limited drug-drug interactions.
Presented by Heather Payne, MBBS, FRCP, FRCR
In a session entitled Clearer Vision chaired by Dr. Bertrand Tombal at the 2021 ANZUP Annual Scientific Meeting, Dr. Heather Payne discussed issues relating to the care of men with metastatic hormone-sensitive prostate cancer (mHSPC).
Presented by Nick James, MBBS, PhD, and Bertrand Tombal, MD, PhD
In this session, Dr. Bertrand Tombal and Dr. Nick James summarized the panel responses to the consensus questions. This was followed by a discussion on the management of metastatic hormone sensitive prostate cancer (mHSPC) with input from the discussants and the panel.
Presented by Ian Davis, MBBS, PhD, FRACP, FAChPM
In this session, Dr. Ian Davis reviewed the evidence for “triplet therapy” comprising ADT plus docetaxel plus additional systemic therapy in metastatic hormone sensitive prostate cancer (mHSPC).
Presented by Karim Fizazi, MD, PhD
In this session, Dr. Karim Fizazi reviewed evidence for “triplet therapy” comprising ADT plus radiation (RT) to the primary plus additional systemic therapy in metastatic hormone sensitive prostate cancer (mHSPC).
Presented by Karim Fizazi, MD, PhD
In this presentation, Dr. Karim Fizazi discussed updated results of PEACE-1, a randomized Phase 3 trial in men with de novo metastatic castration-sensitive prostate cancer (mCSPC). This update focused on the overall survival (OS) for men treated with or without abiraterone plus prednisone (AAP).
Presented by Andrew J. Armstrong, MD
(UroToday.com) In the Proffered Paper Session of the ESMO Annual Congress focusing on prostate cancer, Dr. Andrew Armstrong presented the final overall survival analysis from the ARCHES trial of enzalutamide in men with metastatic hormone-sensitive prostate cancer (mHSPC).
Presented by Peter J. Goebell, MD, PhD
The ESMO 2021 virtual annual meeting’s prostate cancer session included a presentation by Dr. Peter Goebell discussing real-world treatment patterns among patients with metastatic hormone-sensitive prostate cancer (mHSPC).
Presented by Daniel J. George, MD
The ESMO 2021 annual meeting’s prostate cancer session included a presentation by Dr. Daniel George presenting data assessing real-world utilization of advanced therapies by metastatic site and age among patients with metastatic castration-sensitive prostate cancer (mCSPC).
Presented by Christopher Sweeney, MBBS
The treatment for metastatic hormone-sensitive prostate cancer plenary session at the EAU 2021 Annual Meeting included a presentation by Dr. Christopher Sweeney discussing when and how to use systemic treatment for recurrent metastatic hormone-sensitive prostate cancer (mHSPC).
Presented by Declan Murphy, MB, BCH, BaO, FRACS, FRCS
At the European Association of Urology (EAU) 2021 Annual Meeting’s plenary session on the treatment for metastatic hormone-sensitive prostate cancer, Dr. Declan Murphy presented a state of the art lecture on the role of modern imaging for de novo versus recurrent metastatic hormone-sensitive prostate cancer (mHSPC).
Presented by Lisa Horvath, PhD, MBBS, FRACP
 In this summary of the preceding three presentations, Dr. Lisa Horvath showed where each abstract falls within the natural history of prostate cancer. Regarding the first presentation, data on radiographic progression free survival (rPFS) with the addition of abiraterone in de novo mHSPC from the PEACE-1 study, 
Presented by Umang Swami, MD
At the 2021 ASCO Annual Meeting, Dr. Umang Swami and colleagues assessed the real-world utilization of effective combination therapies as first-line treatment in insured patients in the U.S. with mCSPC. The authors performed a retrospective study of the Optum health insurance claims database, which includes patients claims data from both commercially insured and Medicare Advantage populations. 
Presented by Daniel J. George, MD
There are a number of treatment options that have been shown to improve overall survival in mCSPC, including docetaxel and novel hormonal therapies including abiraterone acetate, enzalutamide, and apalutamide. While these agents have proven beneficial in clinical trials, improvement in population-level outcomes depends on their widespread adoption. 
Presented by Stephen J. Freedland, MD
There are a number of treatment options that have been shown to improve overall survival, including docetaxel and novel hormonal therapies including abiraterone acetate, enzalutamide, and apalutamide. While these agents have proven beneficial in clinical trials, improvement in population-level outcomes depends on their widespread adoption. Dr. Freedland presented results of an analysis of Medicare data regarding real-world utilization of these agents in men with mCSPC.
Presented by Andrew J. Armstrong, MD
The phase III ARCHES trial, along with the ENZAMET trial, provided the basis for enzalutamide’s approval in this disease space. However, data from each of these trials have suggested that the benefit of treatment intensification may differ on the basis of disease extent. To explore this further, 
Presented by Arun Azad, MBBS, PhD, FRACP
Enzalutamide plus ADT is approved in the US and Europe to treat castration-resistant prostate cancer and was also recently approved for men with metastatic hormone-sensitive prostate cancer (mHSPC) in the US. In ARCHES, enzalutamide plus ADT reduced the risk of the primary endpoint of radiographic progression-free survival events (by 61%), and improved key secondary endpoints versus placebo plus ADT in men with mHSPC.
Presented by Alicia Morgans, MD, MPH 
In a stand-alone session at this year’s Society of Urologic Oncology (SUO) virtual annual meeting, titled Understanding the Evolving Treatment Landscape in Prostate Cancer: How to Leverage the Latest Advances and Strategies to Optimize Patient Outcomes,
Presented by Ian Davis, MBBS, PhD, FRACP, FAChPM
The 2020 Australian and New Zealand Urogenital and Prostate Cancer Trials Group (ANZUP) Mini Annual Scientific Meeting featured a session on ANZUP trial updates, including an update of the critical Phase III ENZAMET trial provided by Drs. Ian Davis, Arun Azad, and Lisa Horvath.
Presented by Alicia Morgans, MD, MPH
In a session entitled “Sorting Through the Maze of Treatment Options for Metastatic Castration-Sensitive Prostate Cancer”, Dr. Alicia Morgans from Northwestern University presented a plenary talk discussing the treatment considerations for patients who received combination therapy for metastatic castration sensitive prostate cancer (mCSPC).
Presented by Neal D. Shore, MD, FACS
Dr. Shore from the Carolina Urologic Research Center presented a plenary talk discussing the multitude of hormonal treatment options for patients with metastatic castration sensitive prostate cancer (mCSPC). Dr. Shore began by highlighting data from Dr. Huggins seminal work demonstrating that prostate cancer is hormone dependent.
Presented by Neal D. Shore, MD, FACS
Treatment paradigms for patients with metastatic hormone-sensitive prostate cancer (mHSPC) have changed dramatically in the past 4 years. Before 2016, there were no agents with a demonstrated overall survival benefit in this disease space.
Presented by Alok Tewari, MD, PhD
San Francisco, California (UroToday.com) The second case in the challenging cases discussion was that of a 71-year-old man, a former smoker who suffers from hypertension,
Presented by Alicia Morgans, MD, MPH,
San Francisco, California (UroToday.com) As part of the Prostate Cancer Session at the 2020 American Society of Clinical Oncology Genitourinary Cancers Symposium
Presented by Christopher Sweeney, MBBS
Washington, DC (UroToday.com) Renowned medical oncologist Dr. Chris Sweeney provided an overview of the current landscape of metastatic castration sensitive prostate cancer
Presented by Markus Graefen, MD
Athens, Greece (UroToday.com) Markus Graefen, MD, gave an overview of the role of experimental metastases directed therapies in the era of proven life-prolonging drugs
Presented by Syed Adnan Ali, MBBS
Barcelona, Spain (UroToday.com) In the STAMPEDE study, low metastatic burden was determined to be predictive of overall survival (OS) benefit when radiation therapy (RT)
Presented by Martin R. Stockler, MBBS, MSc, FRACP
Barcelona, Spain (UroToday.com) ENZAmet is an international, cooperative group, randomized phase 3 trial. It recently showed that after a median follow-up of 34 months
Presented by Nicholas James, BSc, MB, BS, FRCP, FRCR, PhD
Barcelona, Spain (UroToday.com) Professor Nicholas James presented results from the STAMPEDE trial for the addition of docetaxel to first-line hormonal therapy for patients with
Presented by Andrew J. Armstrong, MD
San Francisco, CA (UroToday.com) Enzalutamide (ENZA) is an androgen receptor signaling inhibitor which inhibits the androgen receptor signaling pathway by blocking the binding of androgen to the androgen receptor as well as inhibition of nuclear translocation of the androgen receptor.1 Enzalutamide has been shown to be effective in improving overall survival in patients with metastatic castration resistant prostate cancer (mCRPC) both before and after chemotherapy.2,3
Presented by Paul L. Nguyen, MD
Barcelona, Spain (UroToday.com) Dr. Nguyen presented a summary of the latest news in the treatment of metastatic hormone-sensitive prostate cancer (mHSPC). Four recent major trials were summarized and discussed in this presentation.
Presented by Silke Gillessen, MD
Barcelona, Spain (UroToday.com) Dr. Silke Gillessen presented the medical oncologist’s perspective on the current and future treatment of prostate cancer. Her talk mainly focused on the role of systemic therapy in metastatic hormone-sensitive prostate cancer (HSPC).
Presented by Andrew J. Armstrong, MD
San Francisco, CA (UroToday.com) The introduction of androgen-axis targeted therapies has drastically altered the landscape of advanced prostate cancer. Abiraterone acetate (AA) and Enzalutamide (ENZA) have been driving the change, and have been utilized in even earlier stages of advanced prostate cancer.
Presented by Neil Rohit Parikh, MD, MBA
San Francisco, CA (UroToday.com) Dr. Parikh discussed that previously published data have suggested there may be a benefit for metastasis-directed therapy in patients with oligorecurrent hormone-sensitive prostate cancer. 
Presented by Celestia Higano, MD
Chicago, IL (UroToday.com) Celestia Higano, MD, gave an excellent talk on the topic of treatment toxicities in patients with metastatic hormone-sensitive prostate cancer (MHSPC). Dr. Higano began with the most important question in this topic, on how to decide which therapy to use in MHSPC. 
Presented by Neeraj Agarwal, MD
Chicago, IL (UroToday.com) Neeraj Agarwal provided a comprehensive overview of the treatment of mHSPC. Three general topics were reviewed – the current standard of care for men with (mHSPC), the role of definitive therapy of primary prostate cancer in the setting of mHSPC, 
Presented by Ulka Vaishampayan, MD
San Francisco, CA (UroToday.com) Dr. Vaishampayan and colleagues presented results of their randomized trial assessing enzalutamide vs bicalutamide in combination with androgen deprivation in metastatic hormone sensitive prostate cancer. 
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