Topic: Metastatic Hormone Sensitive Prostate Cancer

Metastatic Castrate Sensitive Prostate Cancer

Rana McKay, MD, discusses the evolving treatment strategies for metastatic hormone-sensitive prostate cancer (mHSPC), emphasizing advancements over the past decade. In this 20-minute presentation, McKay shares that prostate cancer remains a leading cause of mortality among men. While traditional androgen deprivation therapy (ADT) has long been the cornerstone treatment, newer approaches integrating chemotherapy, androgen receptor signaling inhibitors (ARSIs), and combination regimens have transformed patient outcomes. She refers to landmark studies like CHARTED, LATITUDE, and STAMPEDE, highlighting the benefits of early intensifying treatment and showing significant survival advantages with doublet and triplet therapies. She also shares recent trials, including PIECE-1 and ARASENS, that underscore the effectiveness of adding agents like abiraterone or darolutamide to ADT and docetaxel for high-risk, high-volume disease.

Dr. McKay asserts clinical decision-making now incorporates disease factors such as volume and risk, patient comorbidities, and drug-specific considerations like toxicity profiles and cost. Emerging genomic and molecular tools are poised to refine treatment personalization further, with ongoing trials exploring the optimal integration of novel agents.

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Choosing Systemic Therapy for Men with Metastatic Hormone Sensitive Prostate Cancer

Andrew W. Hahn, MD, analyzes systemic therapy choices for men with metastatic hormone-sensitive prostate cancer. His presentation delves into the critical factors influencing treatment decisions and the latest advancements in therapeutic options.
Dr. Hahn begins by outlining current systemic therapies, including androgen deprivation therapy (ADT) and its combination with other agents. By discussing the mechanisms of action and the efficacy of various therapeutic agents, Dr. Hahn provides a detailed examination of the available treatment options.
Dr. Hahn also addresses the role of personalized medicine in managing metastatic hormone-sensitive prostate cancer. He highlights the importance of genetic profiling and biomarker testing in tailoring treatment plans to individual patients.
Throughout the presentation, Dr. Hahn underscores the dynamic nature of prostate cancer treatment, with ongoing research continually informing and refining clinical practice.

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Management of mHSPC-Singlets and Doublets and Triplets

Alan H. Bryce, MD, discusses metastatic hormone-sensitive prostate cancer (mHSPC) and the importance of early and effective treatment to improve patient outcomes. While singlet therapy, which typically involves androgen deprivation therapy (ADT) alone, has been the traditional approach, newer evidence supports the use of combination therapies.
Data on doublet therapy, combining ADT with either chemotherapy or a novel hormonal agent such as abiraterone, enzalutamide, or apalutamide, have demonstrated significant improvements in overall survival and progression-free survival compared to ADT alone. Key studies, including the LATITUDE and CHAARTED trials, have established the efficacy of these doublet regimens.
Dr. Bryce also explores adding a second novel agent or chemotherapy to the ADT and initial novel agent combination (triplet therapy). He notes that while triplet therapy may offer further survival advantages, it also carries an increased risk of side effects and requires careful patient selection and management.

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GU ASCO Symposium 2022 Summary

Ulka Vaishampayan, MD, Professor of Medicine and Genitourinary (GU) Oncology at the University of Michigan’s Rogel Cancer Center in Ann Arbor, Michigan, discusses highlights from the 2022 GU ASCO Symposium, focusing on advanced prostate cancer treatment research. She begins by discussing the phase 3 ARASENS trial, which looked at overall survival with darolutamide versus placebo in combination with androgen deprivation therapy (ADT) and docetaxel for metastatic hormone-sensitive prostate cancer (mHSPC). Dr. Vaishampayan explains that the investigators found that darolutamide significantly reduced the risk of death by 32.5%, and that this means that an overall survival benefit has now been seen with treatment intensification in 2 separate trials: PEACE-1 (docetaxel plus abiraterone) and ARASENS (docetaxel plus darolutamide). She argues that these results indicate that a triplet regimen with ADT, docetaxel, and darolutamide is the new standard of care in men with mHSPC. Dr. Vaishampayan then moves on to discuss the phase 3 PROpel trial of olaparib and abiraterone versus placebo and abiraterone as first-line therapy for patients with metastatic castration-resistant prostate cancer (mCRPC). She notes that PROpel found 34% risk reduction of progression or death with olaparib plus abiraterone, and that while overall survival data is fairly immature, the trend seems to favor olaparib plus abiraterone over placebo plus abiraterone. She also highlights that the safety profile of olaparib plus abiraterone was consistent with the safety profile for the individual drugs and there was no detriment to quality of life. Finally, Dr. Vaishampayan considers first results from the phase 3 MAGNITUDE study of niraparib with abiraterone acetate and prednisone as first-line therapy in patients with mCRPC with and without homologous recombination repair (HRR) gene alterations. She explains that MAGNITUDE showed a benefit to niraparib in the HRR arm, but no benefit in the non-HRR arm. Dr. Vaishampayan concludes that MAGNITUDE demonstrates the importance of testing for HRR gene alterations in patients with mCRPC to identify who will optimally benefit from the combination of niraparib and prednisone and also supports niraparib plus prednisone as a new first-line treatment option for patients with mCRPC and alterations in genes associated with HRR.

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Standard Treatments and Global Perspective

Marc B. Garnick, MD, the Gorman Brothers Professor of Medicine at Harvard Medical School and the Beth Israel Deaconess Medical Center, summarizes recent developments in nomenclature, disease states, and standard treatments for advanced prostate cancer. Using material from a chapter he wrote for ASCO-SEP with David J. Einstein, MD, Assistant Professor of Medicine at Harvard Medical School, Dr. Garnick begins by considering the new language used to describe different states of advanced prostate cancer, including non-metastatic castrate-sensitive prostate cancer (nmCSPC), non-metastatic castrate-resistant prostate cancer (nmCRPC), metastatic castrate-sensitive prostate cancer (mCSPC), and oligometastatic prostate cancer. He then discusses new standards of care for these different states, highlighting recent research indicating the benefits of using darolutamide, enzalutamide, and apalutamide in the nmCRPC setting, and explaining how to appropriately layer and sequence therapies across disease states. He briefly looks at the role of next-generation sequencing in informing the potential benefit of PARP or PD-L1 inhibitors and touches on bone considerations in mCRPC. Dr. Garnick concludes with some comments on the global inequities of prostate cancer treatment, citing data on the significant disparity in mortality-to-incidence rate of prostate cancer in high-income countries compared to low- to middle-income countries.

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Real World Utilization of Guideline Based Therapy in mCSPC: Update From the 2021 ASCO Annual Meeting

Neeraj Agarwal, MD, Professor of Medicine and Presidential Endowed Chair of Cancer Research at the Huntsman Cancer Institute at the University of Utah in Salt Lake City, examines the underutilization of effective intensified androgen deprivation therapy (ADT) for patients with metastatic castration-sensitive prostate cancer (mCSPC). He begins by emphasizing the unprecedented efficacy of intensified ADT in improving survival for patients with mCSPC. Dr. Agarwal then asserts that, despite those findings, less than a third of patients are being offered intensified ADT therapies as first-line (1L) treatment for mCSPC, even four to five years after data has become available. Dr. Agarwal supports this argument by citing three studies from the 2021 ASCO Annual Meeting: real-world utilization of advanced therapies and racial disparity among patients with mCSPC, a Medicare database analysis of over 35,000 patients (2009-2018); real-world 1L treatment patterns in patients with mCSPC in a U.S. health insurance database (2014-2019); and real-world treatment patterns among patients diagnosed with mCSPC in community oncology settings (2014-2019). Dr. Agarwal summarized the most salient finding: less than one-third of men received intensified treatment (ADT combined with docetaxel or with a novel hormonal therapy) as their first-line treatment for mCSPC. Additionally, most men received ADT alone or ADT combined with a nonsteroidal antiandrogen as their 1L treatment, even as recently as 2019, with Black and Hispanic men even less likely than White men to receive an intensified treatment. Further, most men whose cancer had spread to soft organs (e.g., liver, lungs) had received ADT alone. Dr. Agarwal concludes by reemphasizing that the vast majority of patients are not receiving intensification therapy which is backed by level-one evidence. Dr. Agarwal points to the importance of education, awareness, and access as critical to developing better science around implementation and leading to more patients being able to receive these transformative treatments.

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TITAN Phase 3 Trial with Apalutamide in Metastatic Castration Sensitive Prostate Cancer

Neeraj Agarwal, MD, Professor of Medicine and Presidential Endowed Chair of Cancer Research at the Huntsman Cancer Institute at the University of Utah in Salt Lake City, summarizes results from the phase 3 TITAN trial of apalutamide in metastatic castration-sensitive prostate cancer (mCSPC), focusing on patient-reported quality of life outcomes. He briefly discusses the design of the study, explaining that it featured a 1:1 randomization of over 1000 patients to apalutamide plus ADT or placebo plus ADT and had dual endpoints of overall survival (OS) and radiographic progression-free survival (rPFS). Dr. Agarwal notes that both primary and final analysis found significant improvements in both OS and rPFS. Surprisingly, adjusting for the approximately 40% crossover from the placebo arm to the apalutamide arm actually led to an even greater reduction in risk of death (48% compared to 35%). Dr. Agarwal notes that this is an unprecedented improvement in survival with mCSPC, and also that rapid and deep PSA decline with apalutamide and ADT was associated with improved OS. He also considers quality of life (QoL) measurements, describing the assessment tools for evaluating pain, fatigue, and health-related QoL, and then highlighting that neither primary nor final analysis saw declines in any of these with apalutamide as compared to placebo. In fact, patients on apalutamide reported experiencing less pain. Dr. Agarwal concludes that in men with mCSPC treatment with apalutamide significantly improved survival outcomes without adversely affecting quality of life and fatigue.

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