Clinical Investigators Discuss the Emerging Role of AKT Inhibitors in the Care of Patients with Prostate Cancer — Symposium Video Proceedings

Faculty

TARGET AUDIENCE
This program is intended for urologists, medical and radiation oncologists and other allied healthcare professionals involved in the treatment of prostate cancer.

LEARNING OBJECTIVES

• Appreciate the incidence and clinical relevance of PTEN deficiency in prostate cancer, and understand the optimal method for assessing PTEN status in patients.
• Evaluate emerging Phase III data with combined AKT and androgen biosynthesis inhibition for patients with metastatic hormone-sensitive prostate cancer and PTEN deficiency, and consider the potential role of this form of therapy in the current treatment algorithm.
• Implement a plan of care to recognize and manage side effects and toxicities associated with AKT inhibitors in preparation for their potential availability for patients with prostate cancer.
• Recall the design of ongoing clinical trials evaluating novel AKT inhibitors in combination with standard therapies for metastatic prostate cancer, and appropriately counsel patients about availability and participation.

ACCREDITATION STATEMENT
Research To Practice is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians.

CREDIT DESIGNATION STATEMENT
Video Program: Research To Practice designates this enduring material for a maximum of 1.75 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

AMERICAN BOARD OF INTERNAL MEDICINE (ABIM) — MAINTENANCE OF CERTIFICATION (MOC)
Successful completion of these CME activities, which includes participation in the evaluation component and a post-test, enables the participant to earn up to 1.75 (video) Medical Knowledge MOC points in the American Board of Internal Medicine’s (ABIM) Maintenance of Certification (MOC) program. Participants will earn MOC points equivalent to the amount of CME credits claimed for each activity. It is the CME activity provider’s responsibility to submit participant completion information to ACCME for the purpose of granting ABIM MOC credit.

Please note, these programs have been specifically designed for the following ABIM specialty: medical oncology.

AMERICAN BOARD OF SURGERY (ABS) — CONTINUOUS CERTIFICATION (CC)
Successful completion of these CME activities, which includes participation in the evaluation component and a post-test, enables the learner to earn credit toward the CME and Self-Assessment requirement(s) of the American Board of Surgery’s Continuous Certification program. It is the CME activity provider’s responsibility to submit participant completion information to ACCME for the purpose of granting ABS credit.

Please note, these programs have been specifically designed for the following ABS practice area: complex general surgical oncology.

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HOW TO USE THIS CME ACTIVITY
Video Program: This CME activity consists of a video component. To receive credit, the participant should review the CME information, watch the video, complete the post-test with a score of 80% or better and fill out the evaluation located at ResearchToPractice.com/AUA2025/AKTiProstate/Video/CME.

CONTENT VALIDATION AND DISCLOSURES
Research To Practice (RTP) is committed to providing its participants with high-quality, unbiased and state-of-the-art education and adheres to the ACCME’s Standards for Integrity and Independence in Accredited Continuing Education. Any individuals in a position to control the content of an accredited continuing education activity, including faculty, planners, reviewers and others, are required to disclose all relevant financial relationships with ineligible entities (commercial interests). All relevant conflicts of interest have been mitigated prior to the commencement of this activity. In addition, all activity content is reviewed by RTP scientific staff and an external, independent physician reviewer for fair balance, scientific objectivity of studies referenced and patient care recommendations.

FACULTY — The following faculty reported relevant financial relationships with ineligible entities:

Leonard G Gomella, MD
The Bernard W Godwin Professor of Prostate Cancer
Chairman, Department of Urology
Senior Director, Clinical Affairs, Sidney Kimmel Cancer Center
Enterprise VP for Urology, Jefferson Health
Editor-in-Chief, Canadian Journal of Urology International
Thomas Jefferson University
Philadelphia, Pennsylvania

Advisory Committees: AstraZeneca Pharmaceuticals LP, Ferring Pharmaceuticals, Lantheus, Merck; Patents: Through Thomas Jefferson University.

Evan Y Yu, MD
Section Head, Medical Oncology, Clinical Research Division
Fred Hutchinson Cancer Center
Medical Director, Clinical Research Support
Fred Hutchinson Cancer Research Consortium
Professor of Medicine
Division of Hematology and Oncology, Department of Medicine
University of Washington School of Medicine
Seattle, Washington

Advisory Committees: AstraZeneca Pharmaceuticals LP, Bayer HealthCare Pharmaceuticals, Bristol Myers Squibb, Johnson & Johnson Pharmaceuticals, Lantheus, Loxo Oncology Inc, a wholly owned subsidiary of Eli Lilly & Company, Merck, Oncternal Therapeutics, Tolmar; Contracted Research: Bayer HealthCare Pharmaceuticals, Blue Earth Diagnostics, Dendreon Pharmaceuticals Inc, Lantheus, Merck, Oncternal Therapeutics, Seagen Inc, Tyra Biosciences Inc.

MODERATOR
Daniel George, MD
Eleanor Easley Distinguished Chair
Professor of Medicine, Surgery and Urology
Duke University School of Medicine
ACS Research Professor
Co-Lead, DCI Center for Prostate and Urologic Cancers
Duke Cancer Institute
Durham, North Carolina

Advisory Committees: Astellas, AstraZeneca Pharmaceuticals LP, Bayer HealthCare Pharmaceuticals, Cardinal Health, Novartis, Pfizer Inc; Consulting Agreements: Astellas, AstraZeneca Pharmaceuticals LP, Bayer HealthCare Pharmaceuticals, Bristol Myers Squibb, Exelixis Inc, Johnson & Johnson Pharmaceuticals, Merck, Novartis; Contracted Research: AstraZeneca Pharmaceuticals LP, Bristol Myers Squibb, Corvus Pharmaceuticals, Exelixis Inc, Merck, Novartis, Pfizer Inc; Data and Safety Monitoring Boards/Committees: AstraZeneca Pharmaceuticals LP; Nonrelevant Financial Relationships: IDEOlogy Health, MJH Life Sciences, Targeted Oncology, UpToDate, UroToday.

RESEARCH TO PRACTICE CME PLANNING COMMITTEE MEMBERS, STAFF AND REVIEWERS — Planners, scientific staff and independent reviewers for Research To Practice have no relevant conflicts of interest to disclose.

These educational activities contain discussion of published and/or investigational uses of agents that are not indicated by the Food and Drug Administration. Research To Practice does not recommend the use of any agent outside of the labeled indications. Please refer to the official prescribing information for each product for discussion of approved indications, contraindications and warnings. The opinions expressed are those of the presenters and are not to be construed as those of the publisher or grantor.

These activities are supported by an educational grant from AstraZeneca Pharmaceuticals LP.

Release date: May 2025
Expiration date: May 2026

After completing the post-test, learners may download and review the answers here in order to identify further areas of study.

Dr Gomella

Agarwal N et al. Orteronel for metastatic hormone-sensitive prostate cancer: A multicenter, randomized, open-label phase III trial (SWOG-1216). J Clin Oncol 2022;40(28):3301-9. Abstract

Armstrong AJ et al. Improved survival with enzalutamide in patients with metastatic hormone-sensitive prostate cancer. J Clin Oncol 2022;40(15):1616-22. Abstract

Chi KN et al. Apalutamide in patients with metastatic castration-sensitive prostate cancer: Final survival analysis of the randomized, double-blind, phase III TITAN study. J Clin Oncol. 2021;39(20):2294-303. Abstract

Clarke NW et al. Corrigendum to addition of docetaxel to hormonal therapy in low- and high-burden metastatic hormone sensitive prostate cancer: Long-term survival results from the STAMPEDE trial. Ann Oncol 2020;31(3):442. Abstract

Fizazi K et al. Abiraterone plus prednisone added to androgen deprivation therapy and docetaxel in de novo metastatic castration-sensitive prostate cancer (PEACE-1): A multicentre, open-label, randomised, phase 3 study with a 2 × 2 factorial design. Lancet 2022;399(10336):1695-707. Abstract

Fizazi K et al. Abiraterone acetate plus prednisone in patients with newly diagnosed high-risk metastatic castration-sensitive prostate cancer (LATITUDE): Final overall survival analysis of a randomised, double-blind, phase 3 trial. Lancet Oncol 2019;20(5):686-700. Abstract

Freedland SJ et al. Reasons for oncologist and urologist treatment choice in metastatic castration-sensitive prostate cancer (mCSPC): A physician survey linked to patient chart reviews in the United States. ASCO 2022;Abstract 5065.

Freedland SJ et al. Treatment patterns and survival in metastatic castration-sensitive prostate cancer in the US Veterans Health Administration. Cancer Med 2021;10(23):8570-80. Abstract

Gravis G et al. Burden of metastatic castrate naive prostate cancer patients, to identify men more likely to benefit from early docetaxel: Further analyses of CHAARTED and GETUG-AFU15 studies. Eur Urol 2018;73(6):847-55. Abstract

James ND et al. Abiraterone acetate plus prednisolone for metastatic patients starting hormone therapy: 5-year follow-up results from the STAMPEDE randomised trial (NCT00268476). Int J Cancer 2022;151(3):422-34. Abstract

Kyriakopoulos CE et al. Chemohormonal therapy in metastatic hormone-sensitive prostate cancer: Long-term survival analysis of the randomized phase III E3805 CHAARTED trial. J Clin Oncol 2018;36(11):1080-7. Abstract

Scher HI et al. Trial design and objectives for castration-resistant prostate cancer: Updated recommendations from the prostate cancer clinical trials working group 3. J Clin Oncol 2016;34(12):1402-18. Abstract

Smith MR et al. Darolutamide and survival in metastatic, hormone-sensitive prostate cancer. N Engl J Med 2022;386(12):1132-42. Abstract

 

Dr Yu

Cetintas VB, Batada NN. Is there a causal link between PTEN deficient tumors and immunosuppressive tumor microenvironment? J Transl Med 2020;18(1):45. Abstract

Crabb SJ et al. CAPItello-280: A phase III study of capivasertib and docetaxel versus placebo and docetaxel in metastatic castration-resistant prostate cancer. Genitourinary Cancers Symposium 2023;Abstract TPS287.

Crabb SJ et al. Overall survival update for patients with metastatic castration-resistant prostate cancer treated with capivasertib and docetaxel in the phase 2 ProCAID clinical trial. Eur Urol 2022;82(5):512-5. Abstract

de Bono J et al. IPATential150: Phase III study of ipatasertib (ipat) plus abiraterone (abi) vs placebo (pbo) plus abi in metastatic castration-resistant prostate cancer (mCRPC). ESMO 2020;Abstract LBA4.

Esteban-Villarrubia J et al. Mechanisms of immune evasion in PTEN loss prostate cancer. Immuno 2024;4(4):444-60. Abstract

Gonzalez Velez M et al. Differential impact of tumor suppressor gene (TP53, PTEN, RB1) alterations and treatment outcomes in metastatic, hormone-sensitive prostate cancer. Prostate Cancer Prostatic Dis 2022;25(3):479-83. Abstract

Gupta S et al. Real-world overall survival and treatment patterns by PTEN status in metastatic castration-resistant prostate cancer. JCO Precis Oncol 2024;8. Abstract

Lotan TL et al. PTEN loss detection in prostate cancer: Comparison of PTEN immunohistochemistry and PTEN FISH in a large retrospective prostatectomy cohort. Oncotarget 2017;8(39):65566-76. Abstract

Nizialek E et al. Genomic profiles and clinical outcomes in primary versus secondary metastatic hormone-sensitive prostate cancer. Prostate 2021;81(9):572-9. Abstract

Shore ND et al. A phase I study of capivasertib in combination with abiraterone acetate in patients with metastatic castration-resistant prostate cancer. Genitourinary Cancers Symposium 2021;Abstract 85.

Stopsack KH et al. Oncogenic genomic alterations, clinical phenotypes, and outcomes in metastatic castration-sensitive prostate cancer. Clin Cancer Res. 2020 Jul 1;26(13):3230-3238. Abstract

Turnham DJ et al. The PTEN conundrum: How to target PTEN-deficient prostate cancer. Cells 2020;9(11):2342. Abstract

Zhang J-Y et al. Prognostic value of PTEN in de novo diagnosed metastatic prostate cancer. Asian J Androl 2021;24(1):50-5. Abstract

 

Dr George

Sweeney C et al. Ipatasertib plus abiraterone and prednisolone in metastatic castration-resistant prostate cancer (IPATential150): A multicentre, randomised, double-blind, phase 3 trial. Lancet 2021;398(10295):131-42. Abstract

Turner N et al. Capivasertib and fulvestrant for patients with aromatase inhibitor-resistant hormone receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer: Results from the Phase III CAPItello-291 trial. San Antonio Breast Cancer Symposium 2022;Abstract GS3-04.

Zhang J et al. A phase I study of the pharmacokinetics and safety of ipatasertib, an Akt inhibitor in Chinese patients with locally advanced or metastatic solid tumors. Clin Ther 2025;47(2):128-34. Abstract