abiraterone (AST-2970) / Austhera Biosci - LARVOL DELTA

PK and Dose Escalation and Expansion Study of DST-2970 (clinicaltrials.gov) - P1 | N=26 | Terminated | Sponsor: DisperSol Technologies, LLC | N=54 ➔ 26 | Active, not recruiting ➔ Terminated; Dose escalation portion of the study completed, one expansion cohort was eliminated due to change in standard of care, and the second cohort was not enrolled based on future development considerations.

Enrollment change • Trial termination • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

The struggle is real: Keeping up with the rapidly evolving clinical evidence in urology (Urology Times) - ""Keeping up-to-date is challenging, and rapid progress that is now occurring in our field is truly amazing," writes Michael S. Cookson, MD, MMHC, FACS. Like most of you, I appreciate data-driven approaches to medicine and try, when possible, to adhere to evidence-based medicine. Historically, well-constructed guidelines from trusted, reliable sources have helped provide a good reference for clinical guidance. And in what I will refer to as 'simpler' times, there seemed to be relatively close alignment between the published literature and the updated guidelines."

Online posting

The ACDC-RP Phase II Trial: Understanding the Impact on High-Risk Prostate Cancer, Journal Club - Rashid Sayyid & Zachary Klaassen (Urotoday) - "Zach Klaassen is joined by...to analyze the ACDC-RP Phase II Trial concerning neoadjuvant therapy in high-risk prostate cancer patients. The trial focuses on the combination of cabazitaxel, abiraterone, and leuprolide, examining the high treatment failure rates and mortality in this patient group. The discussion details the trial's design, methodology, endpoints, and safety assessments while emphasizing early treatment intensification."

Video

A 65-Year-Old Man with Prostate Cancer : Episode 7: Role of PARP Inhibitor Plus Abiraterone for Patients With mCRPC (Targeted Oncology) - "A medical oncologist discusses situations in which he might recommend abiraterone alongside a PARP inhibitor as first-line treatment for patients with mCRPC."

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Evaluating Outcomes of Enzalutamide and Abiraterone Co-administration: Insights from the ALLIANCE Trial, Journal Club - Rashid Sayyid & Zachary Klaassen (Urotoday) - "...and Zach Klaassen discuss a study on the efficacy of combining enzalutamide and abiraterone in treating metastatic castration-resistant prostate cancer (mCRPC) patients."

Video

How the TALAPRO-2 Study is Redefining First-line Treatment for Metastatic Prostate Cancer, Journal Club - Rashid Sayyid & Zachary Klaassen (Urotoday) - "...and Zach Klaassen shed light on the TALAPRO-2 study published in The Lancet. This study evaluated the combination of talazoparib, a potent PARP inhibitor, and enzalutamide in treating men with first-line metastatic castration-resistant prostate cancer (mCRPC)."

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Projected Savings for Generic Oncology Drugs Purchased via Mark Cuban Cost Plus Drug Company Versus in Medicare, Journal Club - Rashid Sayyid & Zachary Klaassen (Urotoday) - "...and Zach Klaassen explore a study by Brian Cortese and...regarding potential savings through generic oncology drugs purchased via Mark Cuban's Cost Plus Drug Company (MCCPDC) compared to Medicare. The study focuses on the economic impacts of high-priced generic oncology drugs, the financial toxicity experienced by patients, and how MCCPDC can help mitigate these problems."

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Emmanuel Antonarakis, MD, on Dual Androgen Receptor Inhibition in Metastatic Castration-Resistant Prostate Cancer (MedPageToday) - "A pharmacokinetic analysis found that the clearance rate of abiraterone was two to three times higher when administered with enzalutamide, Michael Morris, MD....As a result of these two negative trials, enthusiasm has diminished for conducting additional studies combining androgen synthesis inhibitors with androgen receptor antagonists. The combination of two androgen-directed agents should not be utilized in clinical practice at this time."

Interview

Effective Treatment Options and Sequencing for Patients With Castration-Resistant Prostate Cancer (Medscape) - "Sandhya Srinivas, MD: Hello. I'm Sandy Srinivas. I'm host of the Medscape InDiscussion podcast series on prostate cancer. Today we're going to be discussing an important topic. All patients with prostate cancer who undergo androgen deprivation therapy will ultimately develop castrate resistance, and that's defined as castrate-resistant prostate cancer (CRPC) - patients having a low level of testosterone and having progressive disease either by prostate-specific antigen (PSA) or by imaging studies....Shilpa Gupta, MD: Thank you...I am really honored to be with you to discuss these topics. I was drawn to oncology because of how dynamic the field was at the time, back in 2011 or so, when newer targeted therapies were coming around, and I wanted something where one could always be learning in the field with new treatment options. Urologic oncology was almost a coincidence. I was working in a prostate cancer lab, and at the time I remember that docetaxel was..."

Audio

Androgen Deprivation Therapy and Prostate Cancer: Bone Health, Survivorship, and Side Effects (Medscape) - "Sandhya Srinivas, MD: Hello. I am Sandy Srinivas and I'm the host of the Medscape InDiscussion podcast series on prostate cancer. Today we want to talk about bone health and survivorship with androgen deprivation therapy (ADT). Bone health is an extremely important topic in men with prostate cancer for two reasons....McKay: We always talk about the purpose of the therapy, the duration and extent of what they're going to be on. A lot of the time, being in clinic is talking about survivorship and talking about how to mitigate the symptoms associated with ADT and maximize quality of life when somebody is on ADT. I like to combine that with talking about bone health. We talk a lot about the metabolic changes that are associated with ADT, the changes that, there's an increased propensity to gain weight, increased propensity to have your cholesterol go up or blood sugar go up."

Audio

Chemotherapy Utilized in Pretreated Metastatic Castration-Resistant Prostate Cancer : Episode 9: Physicians Discuss Targeted Treatment for Prostate Cancer Subtypes (Targeted Oncology) - "In the second article of a 2-part article series, Joshua Lang, MD, and live event participants discuss the role of cabazitaxel for the treatment of patients with prostate cancer who harbor certain mutations or have other factors that make their disease unique."

Media quote

Pembrolizumab/Olaparib vs Next-Generation Hormonal Agents in Previously Treated Patients With Biomarker-Unselected Metastatic Castration-Resistant Prostate Cancer (THE ASCO POST) - "As reported in the Journal of Clinical Oncology by Emmanuel S. Antonarakis, MD, and colleagues, the phase III KEYLYNK-010 trial has shown no improvement in survival outcomes with pembrolizumab/olaparib vs a next-generation hormonal agent (abiraterone or enzalutamide) in previously treated patients with biomarker-unselected metastatic castration-resistant prostate cancer. The trial was stopped for futility at the second interim analysis."

Biomarker

ASCO 2023: Latest in PARP inhibitors in prostate cancer (ecancer) - "Prof Rana McKay...discuss the latest in PARP inhibitors in prostate cancer....They cover the recent FDA approval of olaparib with abiraterone and prednisone (or prednisolone) for adult patients with deleterious or suspected deleterious BRCA-mutated (BRCAm) metastatic castration-resistant prostate cancer (mCRPC)...Prof McKay further talk about testing for BRCA mutations and when to test for it. The panel concludes by discussing their clinical experience in using the available combinations in their daily practice."

Video

Exploring Racial Biases in Clinical Trials: The PANTHER Study's Findings on Prostate Cancer - Daniel George (Urotoday) - "Daniel George and Alicia Morgans explore the groundbreaking results of the PANTHER study. The study addresses an enduring gap in clinical trials concerning black patients, who are disproportionately affected by prostate cancer. The PANTHER study investigates the effects of a novel combination of hormonal therapies, apalutamide and abiraterone, in castrate-resistant prostate cancer. Intriguingly, the study shows that black patients exhibit significantly longer radiographic progression-free survival, time to PSA progression, and overall survival rates compared to their white counterparts. While the cause remains unknown, these findings suggest potential biological differences in the way black patients develop castrate-resistant prostate cancer. The conversation underscores the critical need for diversity in clinical trials, urging active patient recruitment and advocacy, in order to understand potential racial disparities in treatment responses."

Video

Risk of Falls With Newer Antiandrogens for Prostate Cancer (Medscape) - "The risk-benefit ratio of adding a second-generation AA to treatment may be different for a patient who wants to stay alert and sharp to keep a complex job 'versus someone whose primary goal is to see their young children graduate high school,' Alexandra Sokolova, MD...and Julie Graff, MD...write in their editorial."

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Options Post First-Line Progression in mCRPC With HRR Mutations : Episode 2: Olaparib/Abiraterone Shows rPFS Benefit in mCRPC Regardless of HRR Status (Targeted Oncology) - "During a Targeted Oncology Case-Based Roundtable event, Alicia K. Morgans, MD, MPH, discussed results of the phase 3 PROpel trial of patients with metastatic castration-resistant prostate cancer."

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Real-World mCSPC First-Line Treatment Intensification Remains Low (Renal and Urology News) - "However, ADT plus ARPI was the most prescribed regimen in the second and third line across all specialties. Both specialists need to increase adoption of ADT plus ARPI in the first line, Dr Agarwal and colleagues noted....Stephen J. Freedland, MD...called the study findings 'a wake-up call to the urological community....Zachary Klaassen, MD, MSc...observed: 'While further advances are exciting, understanding why most men with mHSPC fail to receive today's standard of care should be at least as important as looking for the next advance.'"

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Impact of Previous Local Treatment on First-line Androgen Receptor Axis Targeted Therapy Response in mCRPC: A Secondary Analysis of the COU-AA-302 Trial - Soumyajit Roy (Urotoday) - "...Alicia Morgans in a discussion on a study analyzing the impact of prior treatments to the prostate on outcomes in patients with metastatic castrate-resistant prostate cancer (mCRPC) treated with abiraterone."

Video

ODAC Decision for Olaparib/Abiraterone in mCRPC Likely to Impact Forthcoming Studies (Targeted Oncology) - "Armstrong: The purpose of the ODAC meeting was to let both parties, the FDA and AstraZeneca, discuss the data from the PROpel study. The FDA had a particular question, which was whether the FDA label for the approval of abiraterone plus olaparib should be restricted only to patients that have a BRCA mutation. They posed that question because the FDA was concerned that there may be groups of patients that are not getting much benefit from the combination, and the combination can have some added [adverse] effects."

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FDA Panel Votes Proposed Olaparib/Abiraterone Indication Should Be Restricted to BRCA-Mutant mCRPC (OncLive) - "'I voted yes [to restrict the indication],' said Christopher Lieu, MD...'The question here is, 'Does [the phase 3 PROpel trial (NCT03732820)] prove that patients with non-BRCA-mutated prostate cancer benefit from olaparib?' And I believe that the answer is, 'We don't know.' There is a concern about the entire class of PARP inhibitors in an unselected population and we see that in other diseases. This is only further supported by the negative results in the BRCA-negative population in the only prespecified study conducted thus far in prostate cancer, the [phase 3] MAGNITUDE study [NCT03748641].'...'The applicants provided clear benefit of olaparib plus abiraterone in patients with the BRCA mutation.' Ashley Rosko, MD...said. '[However], the majority of patients will not carry this mutation. Many of the team that are here on the call, and the applicant as well, indicated this heterogeneity in the disease pathogenesis..."

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SPOP Mutations as First Predictive Biomarker for Treatment Selection in De Novo Metastatic Hormone-Sensitive Prostate Cancer (ASCO Daily News) - "Prostate cancers harboring SPOP mutation exhibit very high androgen receptor transcriptional activity, and patients with SPOP mutated prostate cancer benefit more from ADT in the mHSPC setting and from ARPI in the hormone-refractory setting....More studies are warranted to identify predictive biomarkers and treatment strategies to deliver personalized therapies."

Biomarker • Online posting

Dr. Cookson highlights results of PROpel trial for mCRPC (Urology Times) - "'This trial did not require a biomarker for entry in, so patients were treated with combination therapy or standard care, which would have been the abiraterone alone, to see if there was a benefit,' says Michael S. Cookson, MD, MMHC."

Biomarker • Video

Treatment Intensification in Metastatic Castrate-Sensitive Prostate Cancer - Christopher Wallis & Zachary Klaassen (Urotoday) - "In this discussion, Zachary Klaassen...discuss treatment intensification in metastatic castrate-sensitive prostate cancer (mCSPC). Dr. Klaassen...focus their discussion on several studies in the United States and across the globe that have looked at the real-world utilization of androgen deprivation therapy (ADT) plus other agents in the mCSPC disease space."

Video

Trial to evaluate TKI and abiraterone treatment combination for prostate cancer (Urology Times) - "'If outcomes are improved for patients who take this combination - or in patients whose cancer is still progressing after being treated with hormone-based chemotherapy alone - this could be a big step forward in caring for these patients,' says Moshe Ornstein, MD, MA."

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The Efficacy and Safety of Abiraterone Plus Prednisone, With or Without Radiotherapy, in Addition to Standard of Care (PEACE-1): Journal Club – Christopher Wallis & Zachary Klaassen (Urotoday) - "In this UroToday Journal Club...Zachary Klaassen highlight the PEACE-1 Lancet publication Abiraterone plus prednisone added to androgen deprivation therapy and docetaxel in de novo metastatic castration-sensitive prostate cancer (PEACE-1)..."

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