Can Nectin-4 Expression Predict Response to Bladder Cancer Treatment?

What Are the Implications of These Findings?

“[O]ur study suggests that Nectin-4 amplification is a simple, valuable, and easy-to-implement predictive biomarker for EV in patients with (m)UC. The frequent occurrence of Nectin-4 amplifications in other cancer types suggests that this biomarker is a promising candidate with broader applicability for clinical development of Nectin-4-targeted ADCs in a tumor-agnostic context.”

Choosing the best therapy sequence for (m)UC is crucial, the authors write. Considering Nectin-4 amplifications could inform EV drug development — even at earlier stages of the disease — by defining which patient subgroup has the highest chance for long-term benefit.

The authors acknowledge that the primary limitation of the study is that it is retrospective, using archived primary and metastatic tumor specimens with varying ranges between the time of tumor sampling and start of EV treatment.

“Therefore, our data are hypothesis-generating and prospective confirmation in larger, biomarker-driven trials is mandatory,” the authors wrote.

They note that EV plus pembrolizumab [Keytruda] (EV/P) was recently approved as the new standard of care in first-line treatment for (m)UC, so the predictive value of Nectin-4 amplification in this new treatment setting warrants further research.

Dr. Klümper reports stock and other ownership interests in Bicycle Therapeutics, Pfizer, Daiichi Sankyo/UCB Japan, and Immatics; and honoraria for Astellas Pharma and MSD Oncology; and consulting or advisory roles with Astellas Pharma, MSD Oncology, and Eisai. He reports travel reimbursements from Ipsen, Photocure, and MSD Oncology. Other author disclosures are available with the full text of the paper.