|
|
|
|
|
|
|
PEER-TO-PEER CLINICAL CONVERSATION |
|
|
|
|
|
| Genomic and Clinical Profiles of Rapidly Progressing mCRPC Patients |
| Maha Hussain, MD, FACP, FASCO, MBChB |
| Zachary Klaassen speaks with Maha Hussain about a study examining patients who rapidly progress to metastatic castration-resistant prostate cancer despite treatment intensification. |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Highlights from the 2025 American Society of Clinical Oncology Annual Meeting |
|
|
|
|
| Clinical, Environmental, Genetic, and Genomic Profile of Patients with Rapid Progression to mCRPC |
| Maha Hussain, MD |
| Maha Hussain presented a pilot study analyzing clinical, environmental, and genomic factors in patients with metastatic hormone-sensitive prostate cancer (mHSPC) who rapidly progressed to mCRPC within 14 months of starting therapy. The study found no strong environmental or familial risk patterns, though aggressive disease features and somatic mutations (notably TP53 and PTEN) were common. Further research is needed to clarify underlying drivers of early progression despite intensive treatment. |
|
|
|
|
|
| ‘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 presented data showing that fully automated “one button push” PSMA PET quantification reliably predicts progression-free and overall survival in mCRPC patients treated with 177Lu-PSMA therapy. High PSMA SUVmean and lower total tumor volume, derived automatically, were significantly associated with better outcomes—comparable to manually adjusted methods. |
|
|
|
|
|
| Substudy C of the Canadian Cancer Trials Group IND.234 PC_BETS—A Phase II Study of Darolutamide Selected by Androgen-Receptor ctDNA in Patients with mCRPC After Prior ARPIs |
| Michael Ong, MD, FRCPC |
| Michael Ong presented results from Substudy C of the PC-BETS trial, evaluating darolutamide in mCRPC patients with prior ARPI use, stratified by androgen receptor ctDNA status. Darolutamide showed modest activity overall, with higher clinical benefit in patients with androgen receptor amplification or specific mutations, particularly those with SPOP mutations or >10 AR copies. ctDNA profiling helped identify patients more likely to respond, supporting its use in guiding post-ARPI therapy. |
|
|
|
|
|
|
|
|
|
|
| Substudy G of the CCTG IND.234 PC_BETS (V)—A ctDNA–directed Phase II Study of Carboplatin in Patients with Previously Treated mCRPC
|
| April Rose, MD, PhD, FRCPC
|
| April Rose presented Substudy G of the PC-BETS trial, a ctDNA-guided phase II study evaluating carboplatin in mCRPC patients previously treated with AR-targeted therapies. Carboplatin showed meaningful clinical benefit primarily in patients with DNA damage response (DDR) gene alterations (especially BRCA2), but little to no benefit in biomarker-negative patients.
|
|
|
|
|
|
| Impact of Germline Versus Somatic BRCA Mutation Status on the Efficacy of Rucaparib Versus Physician’s Choice in the TRITON3 Study of Patients with mCRPC |
| Simon Chowdhury, MD |
| Simon Chowdhury presented results from the TRITON3 study showing that rucaparib significantly improved radiographic progression-free survival in patients with mCRPC and BRCA mutations, regardless of whether the mutations were germline or somatic. Both subgroups benefited from rucaparib over physician’s choice therapy, and safety profiles were comparable. |
|
|
|
|
|
| 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 real-world data showing that both microsatellite instability-high (MSI-H) and tumor mutational burden-high (TMB-H) status, as assessed by FoundationOneCDx, predict better outcomes with immune checkpoint inhibitors in patients with mCRPC. Notably, even patients with TMB-H but not MSI-H experienced similar benefits, including longer time to next treatment and overall survival, compared to MSI-H patients. |
|
|
|
|
|
| PRESERVE-006: Phase 1 Study of Gotistobart (BNT316/ONC-392) in Combination with Lutetium Lu 177 Vipivotide Tetraxetan in Patients with mCRPC |
| David Wise, MD, PhD |
| David Wise presented phase 1 results from the PRESERVE-006 trial evaluating gotistobart (a novel anti-CTLA-4 antibody) combined with Lu 177 in mCRPC patients. The combination was well tolerated at doses below 10 mg/kg and showed promising PSA50 responses, outperforming Lu 177 alone. These findings support moving forward with lower gotistobart doses in the ongoing phase 2 study, set to complete enrollment by the end of 2025. |
|
|
|
|
|
| PSMA-Targeted Actinium-225 Therapy in Metastatic Castration-Resistant Prostate Cancer (mCRPC): Baseline and Follow-up PSMA PET Parameters Associated with Outcomes
|
| Valentina Marulanda Corzo, MD
|
| Valentina Marulanda Corzo presented data showing that baseline PSMA PET parameters—especially SUVmean and total tumor volume (TTV)—predict PSA50 response and overall survival in mCRPC patients treated with PSMA-targeted actinium-225 therapy (225Ac-J591). TTV was also linked to higher-grade myelosuppression, but paradoxically to less nausea and xerostomia, likely due to a tumor antigen sink effect.
|
|
|
|
|
|
| Plasma Epigenomic Profiling to Reveal Molecular Correlates of Response and Resistance to 177Lu-PSMA-617 in Metastatic Castration-Resistant Prostate Cancer |
| Jacob Berchuck, MD |
| Jacob Berchuck presented a study showing that plasma epigenomic profiling can identify molecular correlates of response and resistance to 177Lu-PSMA-617 in mCRPC. High circulating tumor DNA (ctDNA) and Wnt pathway activity were linked to poor outcomes, while immune pathway activation and transcriptionally active PSMA (inferred from cfDNA) predicted better response. This liquid biopsy approach may enable real-time, noninvasive prediction of treatment efficacy and resistance, advancing precision medicine for PSMA-targeted therapies. |
|
|
|
|
|
| Assessment of PSMA PET/CT Derived Predictive Markers for 177Lu-PSMA-617 Treatment Outcomes: Results from the U.S. Expanded-Access Program |
| Koichiro Kimura, MD, PhD |
| Koichiro Kimura presented findings from the U.S. Expanded-Access Program showing that quantitative PSMA PET/CT metrics, particularly total tumor SUVmean and total lesion quotient (TLQ), are strong predictors of treatment outcomes in mCRPC patients receiving 177Lu-PSMA-617. Total tumor SUVmean best predicted PSA progression-free survival, while TLQ was most predictive of overall survival, outperforming visual scoring methods. |
|
|
|
|
|
|
|
|
|
|
