Guru P. Sonpavde, MD

Invited discussant Guru P. Sonpavde, MD, Director of the Bladder Cancer Program at Dana-Farber Cancer Institute, said: “Antibody-drug conjugates are a major weapon in the way forward in bladder cancer…. The EV-103 trial evaluated neoadjuvant therapy with enfortumab vedotin-ejfv, one of two antibody-drug conjugates approved to treat bladder cancer.”

Dr. Sonpavde pointed out that more than two-thirds of patients in the trial had T2 disease, and “we don’t know the impact [of enfortumab vedotin] on patients with a higher disease burden. We do know that clinical stage impacts pathologic complete response rate.” He called the 36% pathologic complete response rate and the 50% downstaging rate in cohort H “impressive.”

“There were no new safety signals, and these data support further development. There are now multiple trials evaluating the combination of immune checkpoint inhibitors and enfortumab vedotin in bladder cancer,” he continued.

Better Patient Selection

However, Dr. Sonpavde noted: “We do not know whether this is a good-quality pathologic complete response or just a shallow pathologic complete response, and we don’t know whether it will translate to better long-term outcomes. It would be good to see the pathologic complete response rates reported separately by stage T2, T3, and T4. We need better patient selection, especially in the curative setting.”

Dr. Sonpavde also noted there may be a role for precision medicine with enfortumab vedotin, which targets the Nectin-4 protein, especially in the neoadjuvant setting. “We developed enfortumab in all comers because Nectin-4 expression is seen in almost all patients, but we need a better therapeutic index in the neoadjuvant setting,” he said. “The stakes are higher in this setting, and patients with high Nectin-4 gene expression or the luminal subtype may be more sensitive; we need to aim to cure, not just improve survival outcomes.” 

DISCLOSURE: Dr. Sonpavde reported financial relationships with Astellas Pharma, AstraZeneca, Bavarian Nordic, Bicycle Therapeutics, Bristol Myers Squibb, Debiopharm Group, Eisai, Elsevier, EMD Serono, Exelixis, G1 Therapeutics, Genentech, Gilead Sciences, Infinity Pharmaceuticals, Janssen, Loxo/Lilly, Merck, Mereo BioPharma, Pfizer, QED Therapeutics, Scholar Rock, and Seattle Genetics.