Niklas Klümper, Senior Urology Consultant at the University Medical Center Bonn, shared on X:
“Membranous NECTIN4: a future biomarker to guide treatment selection in urothelial cancer?
Great to see this discussion gaining momentum! Also at Uromigos Live.
The key challenge is identifying patients at high risk of not benefiting durablyfrom EV+pembrolizumab – both perioperatively and in 1L metastatic UC.
Despite remarkable progress, in MIBC ~40 – 50% do not achieve pCR with perioperative EV+P and are at high risk for early relapse! And in 1L mUC median PFS in EV-302 was ~12 months – so many patients have no or not durable disease control!
An increasing body of evidence links low/absent membranous NECTIN4 to lower response rates with EV-based therapy, as summarized in our recent article.
Title: Accumulating Evidence Supports NECTIN4 as a Predictive Biomarker for Enfortumab Vedotin: The Compartment Still Matters
Authors: Niklas Klümper, Jonathan E. Rosenberg, David H. Aggen, Markus Eckstein
But a biomarker becomes truly useful when it changes what we do next.
Importantly, other ADC targets such as TROP2 are broadly expressed in many NECTIN4-low/negative tumors, suggesting a potential alternative ADC strategy:
The goal is not to deny patients effective EV-based treatment – but to identify those who may need a different approach.
Location matters. Biology matters. Treatment selection should follow.”
You can also read:
- Brendan Guercio: Great Insights Into Emerging Therapies for Advanced Urothelial Cancer by David Aggen
- David Aggen: Discussion on Perioperative Enfortumab Vedotin-Based Therapy for MIBC
- FDA Approves Durvalumab Plus Enfortumab Vedotin for Muscle-Invasive Bladder Cancer
