Clinical Advances in Hematology & OncologyHighlights in Metastatic Urothelial Cancer From the European Society for Medical Oncology Congress 2023

Revolutionizing Metastatic Urothelial Carcinoma: Comprehensive Insights from ESMO Congress 2023

The European Society for Medical Oncology Congress 2023 (ESMO) presented groundbreaking advancements in the treatment of metastatic urothelial carcinoma (mUC). This comprehensive summary highlights the key findings from various studies and expert commentary, underscoring the evolving landscape of mUC treatment. These insights reflect significant progress in antibody-drug conjugates, immunotherapy, and targeted therapy, offering new hopes and challenges in the management of this complex cancer.

Key Points:

1. Double Antibody Drug Conjugate (DAD) Trial:
   • Study of sacituzumab govitecan (SG) plus enfortumab vedotin (EV) as second-line therapy for mUC.
   • Demonstrated a 70% objective response rate with manageable toxicities.
   • Commentary: The combination of these ADCs is promising, offering a new approach for treatment-resistant mUC.
2. ICRA Trial Efficacy:
   • Investigated paclitaxel with tremelimumab ± durvalumab after progression on platinum and anti-PD-(L)1 therapy.
   • Confirmed ORR of 26% in one arm, indicating variable efficacy.
   • Commentary: Highlights the potential of combining chemotherapy with immunotherapy in mUC, though results vary across arms.
3. EV-302/KEYNOTE-A39 Study:
   • Phase III study comparing enfortumab vedotin with pembrolizumab (EV+P) versus chemotherapy in untreated la/mUC.
   • Showed significantly improved PFS and OS with EV+P.
   • Commentary: Marks a paradigm shift in treatment, challenging traditional cisplatin eligibility criteria.
4. CheckMate 901 Trial:
   • Nivolumab plus gemcitabine-cisplatin versus gemcitabine-cisplatin alone in previously untreated mUC.
   • Demonstrated superior OS and PFS with the addition of nivolumab.
   • Commentary: First trial to show improved outcomes with this combination, potentially redefining frontline therapy.
5. Phase III THOR Study:
   • Examined erdafitinib vs pembrolizumab in pretreated patients with mUC with FGFR alterations.
   • Showed similar median OS but highlighted the complexity of biomarker identification.
   • Commentary: Emphasizes the importance of personalized medicine and the potential of targeting FGFR mutations.
6. Real-World Efficacy of EV and Avelumab:
   • Assessed outcomes with enfortumab vedotin and avelumab in real-world settings.
   • Confirmed their efficacy in mUC management.
   • Commentary: Reinforces the role of these treatments outside clinical trials, indicating their practical application.
7. Additional Insights from the Congress:
   • The congress emphasized innovative combinations and strategies in mUC treatment.
   • Commentary: Reflects on the importance of integrating new therapies and the ongoing evolution in mUC management.

“This was a remarkable ESMO meeting for bladder cancer. In the frontline setting, it has been decades since we have seen such progress. Not one trial was able to show an improvement over platinum-based doublet. And here we had 2 presentations, one right after the other, that both showed an improvement over platinum.”
– Bradley A. McGregor, MD, Lank Center of Genitourinary Oncology, Dana-Farber Cancer Institute

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