Precision Medicine in Prostate Cancer VL

Tarlatamab Shows Encouraging Activity in Phase 1 Trial in DLL3-Positive Neuroendocrine Prostate Cancer - Rahul Aggarwal

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Rahul Aggarwal presents findings on targeting DLL3 in neuroendocrine prostate cancer. He explains that DLL3 is highly expressed in high-risk neuroendocrine prostate cancer, particularly in the treatment-emergent form seen after androgen deprivation therapy. This Phase 1b study expanded on prior research in small cell lung cancer and included 40 patients with broad inclusion criteria for DLL3 posit...

ctDNA Fraction Predicts Response to Lutetium PSMA in TheraP Trial for mCRPC - Edmond Kwan

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Edmond Kwan discusses his latest research on circulating tumor DNA (ctDNA) as a predictive marker for response to Lutetium PSMA-617 versus cabazitaxel. The Phase II TheraP trial compared these treatments in patients with advanced metastatic castration-resistant prostate cancer, utilizing dual imaging selection. Dr. Kwan highlights that ctDNA fraction, the proportion of tumor-derived DNA in circula...

Integrating Genetic Variants and Clinical Factors for Improved Prostate Cancer Prognostication - Susan Halabi

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Susan Halabi discusses her presentation on prognostic factors in metastatic castration-resistant prostate cancer (mCRPC) based on the Alliance trial. The phase three trial, which enrolled 1,311 patients, compared the effects of enzalutamide alone to enzalutamide combined with abiraterone and prednisone. Despite no difference in overall survival between the treatment arms, Dr. Halabi's team develop...

Olaparib plus Abiraterone Versus Placebo plus Abiraterone in Metastatic Castration-Resistant Prostate Cancer (PROpel): Final Prespecified Overall Survival Results of a Randomised, Double-Blind, Phase...

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PROpel met its primary endpoint showing statistically significant improvement in radiographic progression-free survival with olaparib plus abiraterone versus placebo plus abiraterone in patients with first-line metastatic castration-resistant prostate cancer (mCRPC) unselected by homologous recombination repair mutation (HRRm) status, with benefit observed in all prespecified subgroups. Here we re...

UCHL1: A Potential Biomarker and Therapeutic Target for Neuroendocrine Prostate Cancer - Tanya Stoyanova

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Andrea Miyahira hosts Tanya Stoyanova to discuss her study, published in Cell Reports Medicine, on UCHL1 as a potential biomarker and therapeutic target for neuroendocrine carcinomas, including neuroendocrine prostate cancer. Dr. Stoyanova explains that UCHL1, which has dual functions in protein stability, is highly expressed in neuroendocrine tumors and not in non-neuroendocrine ones. The study f...

The Use of PARP Inhibitors in mCRPC with BRCA1/2 Alterations - Joaquin Mateo

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Alicia Morgans speaks with Joaquin Mateo about his presentation on PARP inhibitors. Dr. Mateo discusses the role of PARP inhibitors in treating metastatic castration-resistant prostate cancer (mCRPC) with BRCA1 or BRCA2 mutations, noting the poor prognosis associated with these mutations but highlighting the effectiveness of PARP inhibitors like olaparib and rucaparib. He explains the differences...

The Adrenal Permissive HSD3B1 Allele: A Decade-Long Journey from Initial Discovery to Proven Clinical Significance in Prostate Cancer - Nima Sharifi

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Alicia Morgans and Nima Sharifi discuss the role of the HSD3B1 gene and its variants in prostate cancer. Dr. Sharifi explains that the adrenal permissive allele of HSD3B1 is common in people of European ancestry and is associated with increased conversion of adrenal androgen precursors to potent androgens like DHT. This allele is linked to faster progression and higher prostate cancer-specific mor...

NePtune Trial: Evaluating Neoadjuvant PARP Inhibition in BRCA-Mutated Prostate Cancer - Rana McKay

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Rana McKay discusses the NePtune study, investigating PARP inhibitors as a neoadjuvant treatment for prostate cancer patients with BRCA1/2 mutations. This study, inspired by the success of PARP inhibitors in metastatic settings and neoadjuvant successes in other cancers, aims to address the aggressive nature of BRCA-mutated prostate cancer earlier in the disease course. With a multi-institutional...

Alpha vs Beta Emitters in Prostate Cancer Radiopharmaceuticals: Energy, Range, and Cytotoxicity - Alan Bryce

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Alicia Morgans interviews Alan Bryce about his session on radiopharmaceutical therapies for mCRPC with bone metastases, focusing on the decision-making between radium-223 and lutetium-177. Dr. Bryce explains the session aimed at practical clinical decision-making, emphasizing the underlying science of radiopharmaceuticals, including the distinctions between alpha and beta emitters and their target...

BRCAAWAY Trial: Impact of Abiraterone and Olaparib Combination in Prostate Cancer - Maha Hussain

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Alicia Morgans interviews Maha Hussain about the BRCAAWAY trial, a phase two study exploring the efficacy of combining abiraterone and olaparib for patients with metastatic castration-resistant prostate cancer harboring BRCA1, BRCA2, or ATM mutations. Highlighting the journey from the inception of the trial to its execution, Hussain delves into the rigorous selection criteria and the strategic des...