The GU25 conference delivered groundbreaking insights into the evolving landscape of genitourinary oncology, highlighting new therapeutic approaches and key clinical trial updates. Here’s a deep dive into some of the most pivotal findings presented at the conference.
Findings: A Phase 1 trial demonstrated that casdatifan, a HIF-2α inhibitor, showed an objective response rate (ORR) of 33% at the recommended Phase 2 dose.
Significance: The drug was effective across all IMDC risk groups, with a low primary progression rate (<10%).
Next Steps: The Phase 3 PEAK-1 trial will compare casdatifan + cabozantinib versus cabozantinib alone in PD-1-treated RCC patients.
Thought Leader Commentary: Experts at the conference emphasized the importance of targeting the HIF-2α pathway in RCC, highlighting its potential to complement existing therapies and improve patient outcomes.
Key Results: The combination of enzalutamide and Lu-PSMA-617 extended overall survival (OS) to 34 months compared to 26 months with enzalutamide alone.
Clinical Impact: This supports earlier integration of PSMA-targeted therapy to enhance survival outcomes.
Thought Leader Commentary: Investigators noted that this study reinforces the need for biomarker-driven treatment selection in mCRPC, ensuring patients derive the most benefit from novel combination strategies.
Response Rate: ORR reached 51.7%, with 15 partial responses but no complete responses.
Survival Data: Median progression-free survival (PFS) of 6.2 months and OS of 15.5 months.
Conclusion: A promising first-line treatment option with sustained clinical benefits.
Long-Term Benefits: PFS of 16.4 vs. 8.3 months, OS of 46.5 vs. 35.5 months with nivolumab + cabozantinib vs. sunitinib.
Implication: Durable benefits across lung, bone, and liver metastases with a favorable safety profile.
Thought Leader Commentary: Clinicians at the conference underscored the sustained efficacy of immunotherapy and VEGF-TKI combinations, advocating for their continued use in first-line RCC treatment.
Key Clinical Findings:
Treatment Response:
Clinical Practice Considerations:
Safety:
OS Impact: 20% reduction in death risk, particularly strong in HRR-deficient patients (HR 0.54).
Clinical Consideration: Toxicity management is key due to higher anemia rates.
Thought Leader Commentary: Experts suggested that HRR deficiency testing should become standard practice to optimize treatment personalization.
Efficacy: ORR of 70% in treatment-naïve patients, with a PFS of 30.3 months.
Next Steps: Warranting Phase 3 trials for potential standard-of-care integration.
Thought Leader Commentary: Researchers emphasized the need to define the ideal sequencing of HIF-2α inhibitors in RCC management.
Key Finding: Lenvatinib + belzutifan demonstrated activity, leading to ongoing Phase 3 trials.
Thought Leader Commentary: The role of Belzutifan in combination therapies continues to generate excitement, with experts advocating for additional trials to refine its use.
Clinical Insight: High baseline KIM-1 levels correlated with worse OS, supporting its role as a prognostic marker.
Predictive Value: Patients with >30% KIM-1 decline at 3 weeks had three times longer OS.
Thought Leader Commentary: Experts noted that KIM-1 could become a pivotal biomarker for risk stratification and treatment decision-making in RCC.
The GU25 conference emphasized significant strides in genitourinary oncology, showcasing novel targeted therapies, combination regimens, and biomarker-driven strategies that are reshaping the treatment paradigm. As these promising therapies progress toward regulatory approval, clinicians and researchers must continue refining patient selection to maximize clinical benefits while mitigating toxicity risks.
Thought Leader Commentary Summary: Across multiple sessions, leading oncologists stressed the importance of personalized medicine, optimal sequencing of novel therapies, and the integration of biomarkers to enhance clinical decision-making.