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Practice Updates in Use of ARIs for Metastatic Prostate Cancer

Case Based Peer Perspectives

Video Series

Phase 3 PEACE-3 Study of Enzalutamide + Ra-223: Safety 

Video content above is prompted by the following:

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Evan Y. Yu, MD, discusses how advances in androgen receptor inhibitors (ARIs) and emerging clinical trial data are shaping personalized treatment strategies for in metastatic hormone-sensitive prostate cancer (mHSPC) and metastatic castration-resistant prostate cancer (mCRPC).

Evan Y. Yu, MD, introduces case 1, a 68-year-old patient with newly diagnosed metastatic hormone-sensitive prostate cancer (mHSPC), highlighting the clinical presentation, diagnostic workup, and treatment considerations for high-volume metastatic disease.

Introduction & Case 1 Presentation: mHSPC

Evan Y. Yu, MD, discusses how the goals of therapy for a patient with newly- diagnosed metastatic hormone-sensitive prostate cancer are to control disease progression, extend survival, maintain quality of life, and delay the transition to castration-resistant prostate cancer.



Newly diagnosed Diagnosed mHSPC: Goals of Therapy

Evan Y. Yu, MD, discusses how systemic therapy options for newly diagnosed metastatic hormone-sensitive prostate cancer include androgen deprivation therapy (ADT) combined with chemotherapy or androgen receptor pathway inhibitors (ARPIs) such as abiraterone or enzalutamide, with the choice of frontline treatment depending on factors such as disease burden and patient characteristics, while also considering the structural and physical differences between these ARPIs, which may influence their efficacy and adverse effect profiles.


Newly Diagnosed mHSPC: First-Line Treatment Options 

Evan Y. Yu, MD, discusses how individualized first-line systemic therapy selection for metastatic hormone-sensitive prostate cancer (mHSPC) involves considering factors such as disease burden, patient performance status, and comorbidities while weighing the pros and cons of current options—such as chemotherapy-sparing regimens, androgen receptor pathway inhibitor (ARPI) selection, and the use of triplet versus doublet combination therapies—to optimize efficacy and minimize adverse effects based on each patient’s unique clinical profile.

Newly Diagnosed mHSPC: Androgen Receptor Pathway Inhibitor Selection  

Evan Y. Yu, MD, discusses how the presentation of a patient with metastatic hormone-sensitive prostate cancer (mHSPC) involves evaluating key clinical features such as disease extent, symptoms, and performance status to guide treatment decisions and the selection of appropriate systemic therapies.

Case 1 Presentation (cont): mHSPC

Evan Y. Yu, MD, discusses how the ARANOTE study, which evaluated androgen deprivation therapy (ADT) plus darolutamide for metastatic hormone-sensitive prostate cancer (mHSPC), aimed to assess the efficacy of this combination therapy in a patient population with newly diagnosed mHSPC. He compares its design and objectives with other established ADT plus androgen receptor pathway inhibitor (ARPI) doublet regimens such as LATITUDE, STAMPEDE D, ENZAMET, ARCHES, and TITAN, and how the study’s results, particularly its efficacy data, compare with those from other trials using abiraterone, enzalutamide, and apalutamide in the first-line setting.

Phase 3 ARANOTE Study of ADT + Darolutamide

Evan Y. Yu, MD, discusses how safety data for first-line androgen deprivation therapy plus androgen receptor pathway inhibitors (ARPI) regimens such as darolutamide, abiraterone, enzalutamide, and apalutamide reveal clinically relevant distinctions in their safety profiles, including the most common and challenging toxicities, incidence of grade 3 or higher adverse events, treatment discontinuations, and potential drug-drug interactions. He highlights key factors that influence treatment choice and disease management in patients with metastatic hormone-sensitive prostate cancer.

Phase 3 ARANOTE Study of ADT + Darolutamide: Safety 

Evan Y. Yu, MD, discusses how community oncologists can critically weigh the evidence from studies on androgen deprivation therapy plus androgen receptor pathway inhibitors regimens by considering factors such as efficacy, safety, patient comorbidities, and treatment preferences, and how the collective trial results guide individualized treatment decision-making to optimize outcomes for patients with metastatic hormone-sensitive prostate cancer.

mHSPC: Applying Data Toward Treatment Decision-Making

Evan Y. Yu, MD, discusses how adding chemotherapy to a doublet regimen for metastatic hormone-sensitive prostate cancer may be considered on an as-needed basis, particularly for patients with high disease burden or rapid progression, while carefully weighing the potential benefits and risks of intensifying therapy.

Adding Chemotherapy for a Patient Receiving ADT + an ARPI

Evan Y. Yu, MD, discusses how the presentation of a patient with metastatic castration-resistant prostate cancer (mCRPC) involves evaluating factors such as disease progression despite androgen deprivation therapy, symptoms, prior treatments, and performance status to guide the selection of appropriate therapeutic strategies for managing this advanced disease state.

Case 2 Presentation: mCRPC

Evan Y. Yu, MD, discusses the therapeutic options for metastatic castration-resistant prostate cancer (mCRPC) included in the  National Comprehensive Cancer Network (NCCN) guidelines, such as abiraterone (ABI) based on the COU-AA-301 trial and enzalutamide (ENZA) based on the AFFIRM trial, highlighting the evidence supporting their use and how these therapies align with the most current NCCN recommendation.

Guideline-Directed Treatment Options: mCRPC

Evan Y. Yu, MD, discusses the design and objectives of the phase 3 PEACE 3 study, which evaluates the combination of enzalutamide (ENZA) and radium-223 (Ra-223) in androgen receptor pathway inhibitor (ARPI)–naive metastatic castration-resistant prostate cancer (mCRPC), focusing on its aim to assess the potential synergistic effects of this combination in improving patient outcomes, including overall survival and bone health.

Phase 3 PEACE-3 Study of Enzalutamide + Ra-223: Design

Evan Y. Yu, MD, discusses the key efficacy findings from the PEACE-3 study, which assessed the combination of enzalutamide (ENZA) and radium-223 (Ra-223) in androgen receptor pathway inhibitor (ARPI)–naive metastatic castration-resistant prostate cancer (mCRPC), focusing on the impact of the combination on radiographic progression-free survival (rPFS) and overall survival (OS), and how these results inform clinical decision-making regarding treatment strategies for mCRPC.

Phase 3 PEACE-3 Study of Enzalutamide + Ra-223: Efficacy Data

Evan Y. Yu, MD, discusses the safety data from the phase 3 PEACE-3 study of enzalutamide (ENZA) combined with radium-223 (Ra-223) for androgen receptor pathway inhibitor (ARPI)–naive metastatic castration-resistant prostate cancer (mCRPC), highlighting key safety outcomes, including the incidence of adverse events, treatment-related toxicities, and any potential concerns related to bone health or hematologic function.

Phase 3 PEACE-3 Study of Enzalutamide + Ra-223: Safety

Phase 3 PEACE-3 Study of Enzalutamide + Ra-223: Safety

EP: 1.Introduction & Case 1 Presentation: mHSPC

EP: 2.Newly diagnosed Diagnosed mHSPC: Goals of Therapy

EP: 3.Newly Diagnosed mHSPC: First-Line Treatment Options

EP: 4.Newly Diagnosed mHSPC: Androgen Receptor Pathway Inhibitor Selection

EP: 5.Case 1 Presentation (cont): mHSPC

EP: 6.Phase 3 ARANOTE Study of ADT + Darolutamide

EP: 7.Phase 3 ARANOTE Study of ADT + Darolutamide: Safety

EP: 8.mHSPC: Applying Data Toward Treatment Decision-Making

EP: 9.Adding Chemotherapy for a Patient Receiving ADT + an ARPI

EP: 10.Case 2 Presentation: mCRPC

EP: 11.Guideline-Directed Treatment Options: mCRPC

EP: 12.Phase 3 PEACE-3 Study of Enzalutamide + Ra-223: Design

EP: 13.Phase 3 PEACE-3 Study of Enzalutamide + Ra-223: Efficacy Data

EP: 14.Phase 3 PEACE-3 Study of Enzalutamide + Ra-223: Safety