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PEER-TO-PEER CLINICAL CONVERSATIONS |
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EZH2 Inhibition Combined with ARPI Evaluated in Patients with Castration-Resistant Prostate Cancer
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Nobuaki Matsubara, MD
Neeraj Agarwal speaks with Nobuaki Matsubara about phase one results for mevrometostat, an EZH2 inhibitor evaluated in combination with continued ARPI therapy in patients with castration-resistant prostate cancer following prior AR pathway inhibitor therapy.
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PSMA-RPT Resistance Mechanisms and Relapse
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Christine Mona, PhD
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| At the 2026 UCSF-UCLA PSMA Conference, Christine Mona reviews key drivers of resistance and relapse after PSMA radioligand therapy, including heterogeneous PSMA expression, PSMA-negative disease, lineage plasticity, and tumor microenvironment factors.
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Large-Scale Analysis Examines Inherited DNA Damage Repair Genes in Advanced Prostate Cancer
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Sofie Tolmeijer, PhD
Sofie Tolmeijer discusses germline DNA damage repair variants in 3,005 patients with metastatic prostate cancer, highlighting clinically relevant alterations and the importance of understanding what current testing platforms may miss.
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| Safety and Pharmacokinetics of Mevrometostat in Combination with Enzalutamide in Patients with Metastatic Castration-Resistant Prostate Cancer
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| Nobuaki Matsubara, MD
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| The combination of mevrometostat and enzalutamide showed manageable safety in mCRPC, and this poster focused on optimizing dosing by giving mevrometostat 875 mg twice daily with food. That lower, food-based dose produced similar drug exposure to the higher fasting dose but with fewer gastrointestinal side effects, especially less diarrhea, and was selected for phase 3 development.
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| PROs in a Randomized Phase 1 Study of Mevrometostat + Enzalutamide Versus Enzalutamide Alone in Patients with mCRPC
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| Neal Shore, MD, FACS
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| Neal Shore discusses a report which found that adding mevrometostat to enzalutamide did not meaningfully worsen overall patient-reported quality of life in mCRPC. The combination showed a longer time to deterioration in some prostate-cancer-specific and social/family well-being measures, while broader FACT-P and FACT-G scores were similar between arms.
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| Emerging Evidence for Sequencing and Combining PSMA-Based Therapies in Prostate Cancer - Beyond the Abstract
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| Sola Adeleke, PhD
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| The review argues that PSMA-targeted treatment is moving from single-agent use toward a more integrated strategy, where sequencing and combinations may deepen and prolong responses. Its main point is that PSMA biology is dynamic, so earlier use, biomarker-guided sequencing, and combinations with AR pathway inhibitors, PARP inhibitors, immunotherapy, docetaxel, or radiotherapy are promising, but survival benefit still needs confirmation in larger trials.
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| Germline and Somatic Genetic Testing in Advanced Prostate Cancer: Practical Considerations and Challenges
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| Channing Paller, MD
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| Channing Paller emphasized that advanced prostate cancer should be approached with both germline and somatic testing, because each captures different actionable biology and germline-only testing can miss important tumor alterations. The practical takeaway was to test metastatic patients for targets such as BRCA1/2 and MSI-H/dMMR/TMB-high, use archival or metastatic tissue when possible, and turn to ctDNA or repeat biopsy when tissue is unavailable or uninformative.
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| The Diversity and Clinical Relevance of Germline DNA Damage Repair Gene Variants in 3005 Patients with Metastatic Prostate Cancer
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| Sofie Tolmeijer, PhD
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| This large ASCO GU 2026 analysis found germline DDR variants in about 9% of men with metastatic prostate cancer, with BRCA2 the most common and most clinically aggressive. It also showed that structural variants are an important part of the germline landscape and that many BRCA2 cases had a second somatic hit, supporting the need for germline testing that can detect large rearrangements as well as small variants.
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