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Highlights from the 2025 European Society for Medical Oncology Annual Meeting |
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| 177Lutetium-PSMA Therapy Neoadjuvant to Stereotactic Ablative Radiotherapy for Recurrent Oligo-Metastatic Hormone-Sensitive Prostate Cancer: a Randomized Phase 2 Trial (LUNAR)
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| Jeremie Calais, MD, MSc, PhD
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| The phase 2 LUNAR trial demonstrated that adding neoadjuvant 177Lu-PSMA (PNT2002) to SBRT in patients with recurrent oligometastatic hormone-sensitive prostate cancer significantly improved progression-free survival and delayed the need for androgen deprivation therapy, with consistent benefit across all subgroups. Treatment was well tolerated, with no grade ≥3 non-hematologic toxicities, and the PSA50 response rate was higher in the combination arm.
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| A Phase I/II Trial of Combined Radium-223 and 177Lu-PSMA-I&T in Patients with mCRPC: First Analysis of the AlphaBet Trial |
| Louise Kostos, MBBS |
| The AlphaBet trial demonstrated that combining 177Lu-PSMA-I&T with radium-223 in patients with mCRPC and bone metastases is safe, well-tolerated, and shows promising antitumor activity. The recommended phase II dose was 55 KBq/kg radium-223 with 7.4 GBq 177Lu-PSMA-I&T, with PSA50 and PSA90 response rates of 55% and 18%, respectively, and a median radiographic PFS of 10 months. |
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| LuPARP: Phase 1 Trial of 177Lu-PSMA-617 and Olaparib in Patients with mCRPC |
| Shahneen Sandhu, MBBS FRACP |
| The LuPARP trial evaluated 177Lu-PSMA-617 combined with olaparib in patients with mCRPC, demonstrating that intermittent dosing of olaparib alongside Lu-PSMA-617 is feasible, safe, and shows promising antitumor activity. At the recommended phase 2 dose, the PSA90 response rate was 55%, median radiographic PFS was 12.8 months, and median OS was not yet reached, with manageable toxicities. |
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| BULLSEYE: 177Lu-PSMA-617 in Oligometastatic Hormone-Sensitive Prostate Cancer
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| Niven Mehra, MD
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| The BULLSEYE trial demonstrated that 177Lu-PSMA-617 significantly improves outcomes in patients with oligometastatic hormone-sensitive prostate cancer, extending median progression-free survival to 18 months versus 5 months with deferred ADT (HR 0.07; p < 0.001). Over half of patients achieved ≥90% PSA decline, with 25% achieving complete biochemical response, while side effects were generally mild and quality of life was maintained.
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| CTC Characteristics Associated with Survival Outcomes in mCRPC in a Randomized Trial of Enzalutamide with or Without 177Lu-PSMA-617 (ENZA-P; ANZUP 1901) |
| Megan Crumbaker, MD |
| The ENZA-P CTC sub-study found that baseline CTC characteristics are prognostic in mCRPC: patients with ≥5 CTCs/mL had worse progression-free and overall survival, independent of treatment. A high PSMA+ CTC fraction (≥50%) predicted shorter survival with enzalutamide alone, but this effect was reduced when 177Lu-PSMA-617 was added, suggesting PSMA+ CTCs may identify patients who benefit from combination therapy. |
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| Major Adverse Cardiovascular Events (MACE) in High-Risk Localized and Metastatic Hormone- Sensitive Prostate Cancer in Four Phase III STAMPEDE Platform Protocol Trials
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| Omar El-Taji, MBChB, MRes, MRCS (Eng)
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| The STAMPEDE pooled analysis found that treatment intensification with docetaxel, abiraterone ± enzalutamide, or radiotherapy in high-risk or metastatic hormone-sensitive prostate cancer did not significantly increase major cardiovascular events. While ARPI addition showed a slight trend toward higher events, overall MACE risk remained manageable. SCORE2 effectively stratified patients but underestimated absolute risk, highlighting the need for careful cardiovascular assessment in high-risk individuals.
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| Machine Learning Prediction of Anemia in Patients with Metastatic Castrate-Resistant Prostate Cancer Treated with Talazoparib + Enzalutamide
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| Ugo De Giorgi, MD, PhD
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| TALAPRO-2 data demonstrated that machine learning models can accurately predict grade ≥3 anemia in mCRPC patients treated with talazoparib plus enzalutamide. Key predictors included older age, Asian race, lower body weight, and recent hemoglobin levels. These models may enable individualized care by guiding early dose adjustments to prevent severe anemia and avoid transfusions or treatment interruptions.
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| Doublet versus Triplet Therapy in High Volume Metastatic Hormone-Sensitive Prostate Cancer Patients with Bone Metastases: Results from the ARON-3 Study
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| Philipp Mandel, MD
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| The ARON-3 study at ESMO 2025 showed that in high-volume mHSPC patients with bone metastases, triplet therapy (ADT + ARPI + docetaxel) led to significantly longer time-to-treatment failure and overall survival compared to doublet therapy (ADT + ARPI) in patients with >10 bone metastases or visceral metastases. No significant survival benefit was observed for patients with ≤10 bone metastases.
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| Phase 1 Trial of ASP5541 (PRL-02), A Long-Acting Intramuscular Depot Injection of Abiraterone Decanoate, in Patients with Advanced Prostate Cancer |
| Jose Avitia, MD |
| The phase I trial of ASP5541, a long-acting intramuscular depot of abiraterone decanoate, demonstrated that 1,260 mg every 84 days effectively suppresses testosterone with low systemic exposure and a favorable safety profile. Deep and durable PSA responses were observed, especially in ARPI-naïve mCRPC patients, with 100% achieving PSA50 and 87.5% achieving PSA90. ASP5541 was well-tolerated, showing low rates of mineralocorticoid toxicity, no significant liver toxicity, and will advance to a phase II study. |
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| Darolutamide Efficacy, Quality of Life, and Safety Outcomes by Age Subgroup: ARANOTE Post Hoc Analyses |
| Fred Saad, MD, FRCS |
| Post hoc analyses from ARANOTE showed that darolutamide + ADT improved radiological progression-free survival, delayed time to mCRPC and PSA progression, and maintained quality of life across all age subgroups in patients with mHSPC. Treatment-emergent adverse events were similar to placebo within each age group, with low discontinuation rates. These findings support darolutamide + ADT as an effective and well-tolerated therapy for mHSPC regardless of patient age. |
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| PSMACare Trial-In-Progress: A Phase II trial of [177Lu]Lu-PSMA-617 with or without ARPI in Patients with PSMA-Positive Nonmetastatic Castration-Resistant Prostate Cancer
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| Fred Saad, MD, FRCSC
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| The PSMACare trial is an ongoing phase II study evaluating [177Lu]Lu-PSMA-617 with or without an ARPI in patients with PSMA-positive non-metastatic castration-resistant prostate cancer (nmCRPC). About 120 patients are being randomized to receive 177Lu-PSMA-617 alone or combined with an ARPI, with ongoing ADT in both arms, and the primary endpoint is PSA response. The study aims to assess whether the combination can safely delay metastatic progression in nmCRPC, with enrollment ongoing across 13 countries.
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