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Highlights from the 2025 European Society for Medical Oncology Annual Meeting |
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| Imaging-Based Theranostics: Is This Really Happening? |
| Louise Emmett, MD, MBChB, FRACP, FAANMS |
| Louise Emmett highlighted that PSMA and FDG PET imaging provide strong predictive and prognostic value for patients receiving PSMA-targeted radioligand therapy, with higher PSMA uptake and tumor homogeneity correlating with better outcomes. She emphasized integrating imaging with molecular biomarkers like ctDNA and PSA to refine treatment personalization and early response assessment. Ongoing efforts such as the SPARC initiative aim to standardize PSMA-PET/CT interpretation, while automated quantification shows promise for consistent, prognostically relevant imaging analysis. |
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| What Is Next After Clinical Trials Testing PSMA & Lutetium-177?
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| Jeremie Calais, MD, MSc, PhD
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| Jeremie Calais outlined how the success of Lu-177–PSMA therapy has transformed prostate cancer care and set the stage for the next generation of radioligand therapies. Ongoing and future studies are moving this approach into earlier disease settings, exploring new radionuclides (like Ac-225 and Pb-212), novel targets (e.g., CAIX, FAP, DLL3), and combination strategies with ARPIs, PARP inhibitors, and immunotherapy to overcome resistance.
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| Scaling up Capacity to Deliver Radioligand Therapeutics
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| Ken Herrmann, MD, MBA
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| Ken Herrmann discussed how to scale up capacity to deliver radioligand therapeutics. The theranostics pipeline has grown exponentially, reflecting the rapid expansion and diversification of agents under development. Multiple pharmaceutical companies, both large and emerging, are now engaged in preclinical and clinical programs targeting a broad range of isotopes and molecular platforms, including peptides, antibodies, small molecules, and mini-proteins.
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| Results from the Phase 1b Dose Escalation of 212Pb-ADVC001 in PSMA-Positive mCRPC: The TheraPb Trial
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| Aaron Hansen, BSc, MBBS, FRACP
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| Aaron Hansen presented the Phase 1b TheraPb trial evaluating ²¹²Pb-ADVC001, an alpha-emitting PSMA-targeted radioligand therapy in mCRPC. The study showed no dose-limiting toxicities and a favorable safety profile, with 80% PSA50 responses and 100% objective responses at doses ≥160 MBq. Imaging confirmed strong tumor uptake with minimal normal organ exposure, supporting further development; Phase 2 will explore 160–200 MBq dosing in chemo-naïve, post-¹⁷⁷Lu-PSMA, and mHSPC populations.
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| Associations Between Quantitative Baseline 68Ga-PSMA-11 PET Parameters and 177Lu-PSMA-617 Efficacy in the PSMAfore Study |
| Ken Herrmann, MD, MBA |
| Ken Herrmann presented a post hoc analysis from PSMAfore, showing that higher baseline whole-body SUVmean on ⁶⁸Ga-PSMA-11 PET was associated with better outcomes in patients treated with ¹⁷⁷Lu-PSMA-617 for PSMA-positive mCRPC. In contrast, higher PSMA-positive tumor volume predicted worse radiographic progression-free and overall survival, regardless of treatment. |
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| Utilizing the CHAARTED and STAMPEDE2 Criteria in the PSMA PET Era: Implications on Outcomes in Metastatic Prostate Cancer |
| Hoda Abdel-Aty, MD |
| Hoda Abdel-Aty presented a retrospective study of 309 patients with PSMA PET–defined metastatic prostate cancer showing that both CHAARTED and STAMPEDE2 disease volume criteria effectively stratified outcomes in the PSMA PET era. Patients with oligometastatic or low-volume disease had significantly longer radiographic progression-free survival and overall survival than those with polymetastatic or high-volume disease. |
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| Combined Treatment with Radium-223 and Enzalutamide in Patients with mCRPC: Insights from the Global REASSURE Study |
| Igle Jan de Jong, MD, PhD, FEBU |
| Igle Jan de Jong presented real-world data from the REASSURE study showing that combining enzalutamide with radium-223 in patients with mCRPC was well tolerated and showed no new safety concerns. Most patients completed radium-223 therapy, and overall survival was longer (19.3 vs 15.6 months) compared to the broader REASSURE cohort. The combination was typically used earlier in the disease course, with low fracture rates supported by the frequent use of bone-protective agents. |
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| LuRa: Efficacy and Tolerability of Radium-223 Following [177Lu]Lu-PSMA-617 in Patients with Metastatic Castration-Resistant Prostate Cancer |
| Jabra Zarka, MD |
| Jabra Zarka presented the LuRa study, evaluating radium-223 after [¹⁷⁷Lu]Lu-PSMA-617 in patients with mCRPC. The sequential approach was feasible and generally well tolerated, with manageable hematologic toxicity and no cumulative marrow suppression observed. While PSA responses were limited, many patients showed reductions in alkaline phosphatase, indicating bone disease control, and some achieved prolonged clinical benefit, supporting this sequential radioligand strategy for selected, bone-predominant mCRPC patients. |
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| Long-Term Adverse Events in PSMA Targeted Radionuclide Therapy for Castration-Resistant Prostate Cancer |
| Aaron Holmes, MD |
| Aaron Holmes presented long-term safety data on PSMA-targeted radionuclide therapy for castration-resistant prostate cancer, analyzing outcomes from 116 patients across 11 prospective trials. Most adverse events were low-grade and not directly linked to PSMA-TRT, with anemia and thrombocytopenia being most common. Only 6% experienced grade 3–4 toxicities attributable to treatment, and while some secondary malignancies were observed, they were rare—supporting PSMA-TRT’s favorable long-term safety but underscoring the need for ongoing follow-up. |
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| Bone Fractures and Prior Abiraterone Use in Men Treated with Radium-223 and Enzalutamide Combination for CRPC with Bone Metastases: A Real-World Observational Study |
| Rana R. McKay, MD |
| Rana R. McKay presented a real-world analysis of men with mCRPC treated with the radium-223 + enzalutamide combination, evaluating the impact of prior abiraterone use on bone fracture risk. Using U.S. insurance claims data (2016–2022), the study found no difference in fracture rates between patients with or without prior abiraterone exposure (both 15%). However, bone health agent use significantly reduced fracture risk. |
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| Real-World Experience with Darolutamide in 799 Patients with nmCRPC: A Prespecified Interim Analysis of the DAROL Prospective Observational Study |
| Murilo de Almeida Luz, MD |
| Murilo de Almeida Luz presented the fourth interim analysis of the DAROL study, evaluating real-world outcomes of darolutamide in 799 patients with nmCRPC. After a median follow-up of 22.5 months, darolutamide showed low rates of adverse events, with no new safety signals and only 9% discontinuations—consistent with ARAMIS trial results. |
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| Baseline Features and MFS by Prior Definitive Treatment in Patients with High‑Risk Biochemically Recurrent Prostate Cancer: EMBARK Post Hoc Analysis
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| Neal Shore, MD, FACS
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| Neal Shore presented a post hoc analysis of EMBARK evaluating metastasis-free survival (MFS) by prior definitive treatment in patients with high-risk biochemically recurrent prostate cancer. Overall, the analysis supports the effectiveness of enzalutamide-based therapy in high-risk biochemical recurrence, independent of prior definitive prostate cancer treatment.
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| Real-World Overall Survival in US-Based Patients with Metastatic Hormone-Sensitive Prostate Cancer (mHSPC) |
| Neeraj Agarwal, MD, FASCO |
| Neeraj Agarwal presented real-world data on overall survival in 9,538 US patients with mHSPC. Median OS ranged from 40–52 months between 2015–2021, with modest variation by race, ethnicity, and de novo status, and 3-year survival rates remained stable over the decade. These findings highlight a persistent gap between clinical trial evidence supporting combination therapy and real-world treatment uptake, underscoring the need to better implement proven therapies in routine practice. |
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