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Peer-To-Peer Clinical Conversation |
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| Phase I Trial Combines ONC-392 with Lutetium-177 for Prostate Cancer |
| David Wise, MD, PhD |
| Tian Zhang speaks with David Wise about a phase I study combining ONC-392 with lutetium-177 vipivotide tetraxetan in metastatic castration-resistant prostate cancer. |
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Highlights from the 2025 American Society of Clinical Oncology Annual Meeting |
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| CheckPRO Trial, a Randomized Phase 2 Trial of Nivolumab and Ipilimumab with or Without Stereotactic Body Radiation Therapy in mCRPC |
| Rikke Eefsen, MD, PhD |
| The CheckPRO phase 2 trial evaluated nivolumab and ipilimumab with or without stereotactic body radiation therapy (SBRT) in patients with metastatic castration-resistant prostate cancer (mCRPC) who had progressed on prior therapies. While both treatment arms showed modest PSA and objective response rates (~20%), the addition of SBRT did not improve progression-free or overall survival, and immune-related toxicity remained considerable. |
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| Final PROs in Unselected Men Receiving Talazoparib + Enzalutamide Versus Placebo + Enzalutamide as Initial Treatment for mCRPC: Results from the Phase 3 TALAPRO-2 Study |
| Nobuaki Matsubara, MD |
| In the phase 3 TALAPRO-2 trial, adding talazoparib to enzalutamide in unselected men with mCRPC significantly improved radiographic progression-free survival without compromising patient-reported quality of life. Final results showed no clinically meaningful differences in functioning, symptoms, or pain compared to placebo + enzalutamide, with slightly longer time to definitive deterioration in global health status. |
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| ‘One Button Push’ Fully Automated PSMA PET Quantification: Correlation with Progression Free and Overall Survival in Patients Undergoing 177Lu PSMA Therapy for mCRPC |
| Louise Emmett, MBChB, FRACP, FAANMS, MD |
| Louise Emmett demonstrated that fully automated “one button push” PSMA PET quantification reliably predicts progression-free and overall survival in mCRPC patients receiving 177Lu PSMA therapy. Both SUVmean and total tumor volume—calculated without manual input—strongly correlated with improved outcomes, validating this approach as a practical and scalable clinical tool. |
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| Additive Clinical Utility of Tissue Biomarkers of Microsatellite Instability Status and Tumor Mutational Burden to Predict Immune Checkpoint Inhibitor Effectiveness for Real-World Patients with mCRPC |
| Nicolas Sayegh, MD |
| Nicolas Sayegh presented data from a real-world mCRPC cohort showing that microsatellite instability-high (MSI-H) and/or tumor mutational burden-high (TMB-H) status significantly predict better outcomes from immune checkpoint inhibitor (ICI) therapy. In particular, both MSI-H/TMB-H and non-MSI-H/TMB-H groups had improved time to next treatment and overall survival compared to biomarker-negative patients. |
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| PRESERVE-006: Phase 1 Study of Gotistobart (BNT316/ONC-392) in Combination with Lutetium Lu 177 Vipivotide Tetraxetan in Patients with mCRPC
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| David Wise, MD, PhD |
| David Wise presented promising phase 1 safety and activity data from PRESERVE-006, evaluating gotistobart (BNT316/ONC-392)—a novel anti-CTLA-4 antibody—in combination with Lu 177 vipivotide tetraxetan in metastatic castration-resistant prostate cancer (mCRPC). The combination was generally well tolerated at lower doses and showed signs of enhanced PSA responses compared to Lu 177 monotherapy. |
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| Survival and Hospitalizations with 177Lu-PSMA-617 in Veterans with Underlying Genomic Alterations |
| Sumrah Khan, DO |
| Sumrah Khan presented a retrospective VHA study showing that U.S. veterans with mCRPC treated with 177Lu-PSMA-617 had a median overall survival of 11.4 months, with significantly worse outcomes in those harboring tumor suppressor gene alterations (5.8 vs. 18.0 months; adjusted HR 3.0). While age was not linked to survival or hospitalization, comorbidity burden and genomic alterations were strong predictors of poorer outcomes, suggesting a need for more personalized treatment approaches. |
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| Plasma Epigenomic Profiling to Reveal Molecular Correlates of Response and Resistance to 177Lu-PSMA-617 in Metastatic Castration-Resistant Prostate Cancer |
| Jacob E Berchuck, MD |
| Jacob Berchuck presented a plasma epigenomic profiling study showing that liquid biopsy-based cfDNA analysis can identify molecular predictors of response and resistance to 177Lu-PSMA-617 in mCRPC. High ctDNA burden was linked to worse outcomes, while transcriptionally active PSMA, immune-related pathways, and low Wnt pathway activity were associated with better responses. This approach highlights the potential of minimally invasive, real-time tumor monitoring to guide precision treatment in prostate cancer. |
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| Comparative Effectiveness of Cabazitaxel vs. Lutetium Lu-177 Vipivotide Tetraxetan in Patients with Metastatic Castration-Resistant Prostate Cancer (mCRPC) |
| Zeynep Ozay, MD |
| Zeynep Ozay presented a large real-world analysis comparing cabazitaxel vs. 177Lu-PSMA-617 in mCRPC patients who had progressed on ARPI and docetaxel. Patients treated with 177Lu-PSMA-617 had significantly longer time to next therapy and overall survivalcompared to those receiving cabazitaxel. These results suggest 177Lu-PSMA-617 may offer superior outcomes in this setting, though the study's retrospective design and non-randomized nature warrant caution |
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| Radioligand Therapies in Prostate Cancer: Hits, Misses, and Next Steps |
| Jorge A. Garcia, MD, FACP |
| Jorge Garcia delivered a comprehensive overview on the progress and future of PSMA-targeted radioligand therapy (RLT) in prostate cancer, emphasizing both its clinical promise and current limitations. While 177Lu-PSMA-617 has shown validated efficacy in mCRPC across multiple phase II/III trials and has improved quality of life in later-line settings, challenges remain related to imaging interpretation, patient selection, biologic resistance, and PSMA heterogeneity. |
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| First-in-Human Results of Terbium-161 161Tb-PSMA-I&T Radioligand Treatment in Patients with Metastatic Castration-Resistant Prostate Cancer (VIOLET): A Single-Centre, Single-Arm, Phase I/II Study |
| Michael Hofman, MBBS, FRACP, FAANMS, FICIS, GAICD |
| The VIOLET trial presented the first-in-human results of terbium-161 (¹⁶¹Tb)-PSMA-I&T radioligand therapy in patients with metastatic castration-resistant prostate cancer (mCRPC), showing a favorable safety profile and promising efficacy. In this single-arm phase I/II study, 70% of patients completed all six treatment cycles, with a PSA50 response rate of 70% and median radiographic progression-free survival of 11 months, and no dose-limiting toxicities observed. |
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| Predictive and Prognostic Value of Baseline PSMA-PET Total Tumor Volume and SUV Mean Within ENZA-P, a Randomized Phase II Trial of Enzalutamide Versus Enzalutamide plus [177Lu] Lu-PSMA-617 (ANZUP1901) |
| Louise Emmett, MD, FRACP, MBChB |
| The ENZA-p phase II trial showed that baseline PSMA total tumor volume (TTV) is a strong predictor of overall survival and PSA response in metastatic castration-resistant prostate cancer patients treated with enzalutamide alone. Importantly, adding [177Lu] Lu-PSMA-617 radioligand therapy mitigates the negative impact of high tumor burden, improving survival outcomes. SUVmean was not a reliable prognostic marker in this setting. |
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| Radioligand Therapy Remix: Finding the Right Patient for the Perfect Track
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| Jeremie Calais, MD, PhD
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| Jeremie Calais delivered a presentation titled: Radioligand Therapy Remix: Finding the Right Patient for the Perfect Track. Dr. Calais emphasized that the variability in patient responses to Lutetium-PSMA therapy reflects the underlying biological heterogeneity of metastatic prostate cancer. He proposed that distinct patterns of response should be recognized and interpreted in clinical context.
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| How to Get Lutetium-177 PSMA to Those That Will Most Benefit? |
| Ruben Raychaudhuri, MD |
| Ruben Raychaudhuri highlighted the importance of PSMA PET imaging for selecting metastatic castration-resistant prostate cancer (mCRPC) patients who will benefit most from Lutetium-177 PSMA (LuPSMA) therapy, which has shown improved survival and response rates in trials like VISION and TheraP. Despite promising efficacy, challenges remain in optimal treatment sequencing, earlier use, and expanding access due to complex delivery logistics, with ongoing research exploring combination therapies and dosing strategies to enhance outcomes. |
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