Topic: Metastatic Castration Resistant Prostate Cancer

How to Best Select Doublet vs. Triplet Therapy in MCSPC

Scott B. Sellinger, MD, FACS, addresses key considerations in deciding between doublet and triplet therapies for metastatic castration-sensitive prostate cancer.

In this 12-minute presentation, Dr. Sellinger highlights the superiority of androgen deprivation therapy (ADT) combined with androgen pathway inhibitors. He discusses evidence from pivotal trials, including TITAN, ARCHES, PEACE-1, and ARASENS, demonstrating that doublet and triplet therapies offer superior survival benefits compared to ADT alone.

Sellinger emphasizes that selecting between doublet and triplet therapy is both an art and a science, balancing clinical guidelines with patient-specific factors such as age, comorbidities, and access to treatment. While higher volume and symptomatic patients might benefit from more intensive triplet therapy, the importance of patient preference, PSA response, and cost considerations is underscored. He suggests that establishing clearer guidelines on doublet versus triplet therapy could help practitioners make more confident decisions for their patients in this nuanced field.

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Novel Ways of Targeting the Androgen Receptor

Daniel P. Petrylak, MD, explores novel approaches for targeting the androgen receptor (AR) in prostate cancer, highlighting that around 90% of prostate cancer specimens express the androgen receptor, which persists through castrate resistance.

In this 7-minute talk, Dr. Petrylak focuses on targeting the AR ligand-binding domain with molecules known as proteolysis-targeting chimeras (PROTACs). Laboratory findings reveal that PROTACs can degrade AR variants resistant to traditional therapies like enzalutamide, showing efficacy against androgen gene amplification mutations.

He shares that ARV-110, a PROTAC developed for clinical use, showed promise in phase 1 trials with castration-resistant prostate cancer patients. However, due to significant side effects, the ARV-110 trials were abandoned in favor of a newer compound, ARV-766. While ARV-110 has demonstrated efficacy in castration-resistant prostate cancer, ARV-766 offers a broader range of AR degradation with improved patient tolerance, making it the preferred candidate for continued clinical evaluation.

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PARPi in mCRPC

Daniel P. Petrylak, MD, Yale University Cancer Center, New Haven, Connecticut, summarizes the current and future role of PARP inhibitors in mCRPC, providing valuable insights into their clinical application and potential to improve patient outcomes.

In this 9-minute presentation, Dr. Henderson highlights direct costs such as medications, hospital stays, and physician fees, as well as indirect costs including lost income and travel expenses. He emphasizes that these financial strains can lead to treatment non-adherence, delayed care, and worsened clinical outcomes.

Dr. Henderson discusses various strategies and interventions to address these challenges, underscoring the importance of policy changes at the institutional and governmental levels to improve access to affordable care.

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Understanding Metastatic Castration-Resistant Prostate Cancer

Shell Liang, PhD, discusses metastatic castration-resistant prostate cancer (mCRPC), a form of prostate cancer that progresses despite androgen deprivation therapy (ADT). Dr. Liang emphasizes the critical need for advanced therapeutic strategies to manage this aggressive cancer subtype effectively.
The presentation reviews the current therapeutic landscape for mCRPC, focusing on second-generation AR pathway inhibitors such as abiraterone and enzalutamide. Additionally, the discussion includes the role of chemotherapeutic agents like docetaxel and cabazitaxel. Dr. Liang also explores emerging treatment modalities, including PARP inhibitors and immunotherapies.
Dr. Liang advocates using genomic profiling to identify actionable mutations and tailor treatments to individual patient profiles. This approach aims to optimize therapeutic efficacy and minimize adverse effects, aligning with the principles of precision medicine.

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Metastatic Castrate-Resistant Prostate Cancer: Options and Possible Sequences

Dr. A. Oliver Sartor outlines the available therapeutic options for metastatic castrate-resistant prostate cancer (mCRPC), which include novel hormonal agents, chemotherapy, immunotherapy, and targeted therapies. He addresses androgen receptor signaling inhibitors such as abiraterone acetate and enzalutamide, and the use of chemotherapy agents like docetaxel and cabazitaxel.

Dr. Sartor also addresses the emerging role of immunotherapy in mCRPC, particularly with agents like pembrolizumab for patients with specific genetic mutations or microsatellite instability. Additionally, he discusses the potential of radionuclide therapies, such as radium-223.

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New Standards of Care for Advanced Prostate Cancer

In this 20-minute presentation, William K. Oh, MD, Chief of the Division of Hematology and Medical Oncology at the Mount Sinai Health System and Deputy Director of The Tisch Cancer Institute at the Icahn School of Medicine at Mount Sinai, addresses new standards of care in 2021 for advanced prostate cancer and focuses on non-metastatic castration-resistant prostate cancer (nmCRPC), concluding that apalutamide, enzalutamide, and darolutamide improve MFS in men with nmCRPC by ~2 years; SPARTAN, PROSPER, and ARAMIS established favorable benefit-risk for patients with nmCRPC and PSADT<10 months; and these studies provide the best evidence supporting early treatment. He also focuses on metastatic, hormone-sensitive prostate cancer (mHSPC) and concludes that upfront treatment with either abiraterone + prednisone, apalutamide, enzalutamide, or docetaxel is the standard of care and he asserts that new evidence from PEACE-1 and ARASENS supports triple therapy with a novel hormonal therapy +ADT+docetaxel for chemotherapy patients.

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