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GU Cancer Researchers Discuss Latest Breakthroughs at #GU25

Picture of Brian Shields Brian Shields : Feb 27, 2025 7:10:55 AM

KOL #gu25 TALAPRO-2 NIAGARA
GU Cancer Researchers Discuss Latest Breakthroughs at #GU25
Breakthroughs in Genitourinary Oncology: Insights from GU25

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.

1. ARC-20 Trial: Casdatifan in Clear Cell RCC

  • 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.


2. ENZA-P Trial: Enzalutamide + Lu-PSMA-617 in mCRPC

  • 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.


3. EPIC-A Trial: Cemiplimab + Chemotherapy in Penile Cancer


4. CheckMate 9ER: 5-Year Follow-Up in RCC

  • 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.


5. NIAGARA Trial: Perioperative Durvalumab in Bladder Cancer

Key Clinical Findings:

  • Perioperative durvalumab + neoadjuvant chemotherapy improved:
    • Event-free survival (HR 0.68, 95% CI 0.56-0.82)
    • Overall survival (HR 0.75, 95% CI 0.59-0.93)
    • Reduced risk of metastases/death by 33% (HR 0.67, p<0.001)
    • Reduced bladder cancer mortality by 31%

Treatment Response:

  • Higher pathologic complete response (pCR) rate (+10%) with durvalumab arm
  • Benefits seen regardless of pCR status
  • 92% event-free survival at 24 months in pCR patients

Clinical Practice Considerations:

  • Need to evaluate durvalumab+gemcis vs ddMVAC followed by adjuvant nivolumab
  • Question remains if pCR patients after gemcis+durvalumab need adjuvant durvalumab
  • Risk-adapted approach using ctDNA being evaluated in ongoing MODERN trial

Safety:

  • Immune-related adverse events were mostly low grade and consistent with known durvalumab profile


6. TALAPRO-2 Trial: Talazoparib + Enzalutamide in mCRPC

  • 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.


7. LITESPARK-003: Belzutifan + Cabozantinib in ccRCC

  • 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.

8. KEYMAKER-U03: Pembrolizumab + Lenvatinib & Other RCC Combinations

  • 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.


9. CheckMate 214: KIM-1 as a Prognostic Biomarker in RCC

  • 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.


10. TROPiCS-04: Sacituzumab Govitecan in Urothelial Cancer

  • Primary Endpoint: Overall survival (OS) endpoint was not met
  • Key Efficacy Results:
    • Sacituzumab Govitecan (SG) showed higher ORR: 23%
    • Taxane/vinflunine showed ORR: 14%
  • Safety Concerns:
    • G-CSF primary prophylaxis was only used in ~20% of cases
    • Grade 5 neutropenic events were observed in the SG arm


Final Thoughts

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.