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Highlights from the 2025 European Society for Medical Oncology Annual Meeting
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| ENZARAD (ANZUP 1303) Randomized Phase III Trial of Androgen Deprivation Therapy with Radiation Therapy with or without Enzalutamide for High Risk, Clinically Localized Prostate Cancer |
| Paul Nguyen, MD, MBA
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| Paul Nguyen presented results from the phase III ENZARAD (ANZUP 1303) trial, which tested adding enzalutamide to standard ADT and radiation in men with high-risk, localized prostate cancer. The study found no significant improvement in metastasis-free survival overall, though patients with regional lymph node involvement or planned pelvic radiotherapy appeared to benefit.
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| ENZARAD Randomized Phase III Trial Discussion: ADT with Radiation Therapy with or without Enzalutamide for High Risk, Clinically Localized Prostate Cancer (ANZUP 1303) |
| Nicholas James, MBBS, PhD
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| Nicholas James discussed the ENZARAD (ANZUP 1303) trial, noting that while enzalutamide added to ADT and radiotherapy did not improve metastasis-free or overall survival, outcomes were already excellent, suggesting possible overtreatment in this lower-risk cohort. Compared with STAMPEDE M0, ENZARAD enrolled less advanced patients, explaining the differing results and limited treatment effect.
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| Final Results from PRESTO (AFT-19): A Phase 3 Open-label Study of Combined Androgen Blockade in Patients with High-Risk Biochemically Relapsed Prostate Cancer
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| Rahul Raj Aggarwal, MD
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| Rahul Aggarwal presented final results from the phase III PRESTO (AFT-19) trial in men with high-risk, biochemically recurrent prostate cancer. A 12-month course of ADT plus apalutamide significantly improved metastasis-free survival, time to castration resistance, and time to subsequent therapy compared to ADT alone, while adding abiraterone provided no additional benefit but increased toxicity.
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| Phase III EMBARK Trial Overall Survival Results |
| Neal Shore, MD, FACS
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| Final results from the phase III EMBARK trial showed that enzalutamide + leuprolide significantly improved overall survival in patients with high-risk biochemically recurrent prostate cancer, reducing the risk of death by over 40% versus leuprolide alone. Enzalutamide monotherapy showed a trend toward improved survival but did not reach statistical significance. Both enzalutamide regimens also significantly delayed PSA progression, need for new therapy, skeletal events, and disease progression, with no new safety concerns reported.
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| EMBARK and PRESTO Trials Discussion |
| Derya Tilki, MD
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| Derya Tilki discussed the EMBARK and PRESTO phase III trials, both evaluating treatment intensification in high-risk biochemically recurrent prostate cancer. She highlighted that enzalutamide + ADT significantly improved metastasis-free and overall survival in EMBARK, establishing it as a new standard of care, while PRESTO supported a class effect favoring doublet therapy over ADT alone. Tilki emphasized the potential of integrating PSMA PET and metastasis-directed therapy (MDT) to further improve outcomes and prolong treatment-free intervals, warranting future prospective trials.
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| A Phase III Study of Capivasertib + Abiraterone versus Placebo + Abiraterone in Patients with PTEN-deficient De Novo Metastatic Hormone-sensitive Prostate Cancer (mHSPC): CAPItello-281
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| Karim Fizazi, MD, PhD
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| The CAPItello-281 phase III trial demonstrated that adding capivasertib to abiraterone significantly improved radiographic progression-free survival (rPFS) in patients with PTEN-deficient de novo metastatic hormone-sensitive prostate cancer, with a median rPFS of 33.2 vs 25.7 months. Secondary endpoints, including time to castration resistance and symptomatic skeletal events, also favored capivasertib, particularly in patients with higher degrees of PTEN loss.
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| CAPItello-281 Phase III Study Discussion: Capivasertib + Abiraterone versus Placebo + Abiraterone in Patients with PTEN-deficient De Novo mHSPC |
| Elena Castro, MD, MS, PhD
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| Elena Castro highlighted that CAPItello-281 confirms the poor prognosis of PTEN-deficient de novo mHSPC and demonstrates a distinct progression pattern, with some patients experiencing clinical/radiographic progression before PSA rises. The trial met its primary endpoint, showing that capivasertib + abiraterone significantly prolongs rPFS, though overall survival data remain immature and the magnitude of benefit may not yet warrant a change in practice.
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| Phase III Trial of [177Lu]Lu-PSMA-617 Combined with ADT + ARPI in Patients with PSMA-Positive Metastatic Hormone-Sensitive Prostate Cancer (PSMAddition) |
| Scott Tagawa, MD, MS, FACP, FASCO |
| Scott Tagawa presented PSMAddition, a phase III trial showing that adding [177Lu]Lu-PSMA-617 to ADT + ARPI significantly improves radiographic progression-free survival in patients with PSMA-positive metastatic hormone-sensitive prostate cancer, with benefits consistent across subgroups. Secondary endpoints—including PSA response, time to mCRPC, and PFS—also favored the combination, while overall survival showed a positive trend. |
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| PSMAddition Phase III Trial Discussion: [177Lu]Lu-PSMA-617 Combined with ADT + ARPI in Patients with PSMA-Positive mHSPC |
| Arun Azad, PhD, MBBS, FRACP
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| Arun Azad noted that PSMAddition showed a significant rPFS benefit with early use of [177Lu]Lu-PSMA-617 in PSMA-positive mHSPC, but overall survival improvement is not yet demonstrated and treatment is associated with higher toxicity and lower quality of life. He emphasized the need for biomarker-driven patient selection, avoidance of overtreatment, and careful monitoring of late toxicities, concluding that widespread use in mHSPC is not currently recommended, though the agent remains effective in mCRPC.
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| Targeting Androgen Receptor Alterations in Prostate Cancer |
| Alice Bernard-Tessier, MD |
| Alice Bernard-Tessier highlighted that androgen receptor alterations—including amplifications, splice variants, and ligand-binding domain mutations—remain highly prevalent in advanced prostate cancer and drive resistance to current AR-targeted therapies. She reviewed emerging strategies, including AR degraders, N-terminal domain inhibitors, and CYP11A1 inhibitors, which show promising activity in mCRPC, particularly in patients with AR mutations, though safety and patient selection remain key challenges. |
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| Optimizing Patient Selection for Radioligand Therapy in Advanced Stages |
| Ken Herrmann, MD, MBA |
| Ken Herrmann emphasized that optimizing patient selection for 177Lu-PSMA-617 radioligand therapy in advanced prostate cancer relies on integrating PSMA PET imaging, tumor volume, and clinical biomarkers. Key predictors of response and survival include baseline PSMA SUVmean, total tumor volume, FDG-derived tumor volume, and ctDNA fraction, with higher tumor burden and ctDNA associated with worse outcomes. |
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| Exploiting Homologous Recombination Alteration Across the Spectrum Disease Stages |
| Neeraj Agarwal, MD, FASCO |
| Neeraj Agarwal highlighted that homologous recombination repair (HRR) gene alterations are present in ~25–30% of advanced prostate cancers and are critical for PARP inhibitor therapy selection across disease stages. ARP inhibitors are a precision therapy targeting HRR alterations, with combination strategies expanding their potential benefit across prostate cancer stages. |
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| Aggressive Variant Prostate Cancers |
| Ana Aparicio, MD |
| Ana Aparicio highlighted that aggressive variant prostate cancer is characterized by combined tumor suppressor defects, androgen indifference, and poor outcomes, with patients benefiting from platinum-based chemotherapy and emerging combinations such as αPD1 + PARP inhibitors. Clinical trials, including C3NIRA and phase I/II carboplatin-cabazitaxel studies, show improved progression-free and overall survival with combination strategies. |
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