Enfortumab vedotin shows anti-tumor activity but does not meet trial goals | ASCO 2024

Background

Enfortumab vedotin is an antibody drug-conjugate (ADC) used to treat urothelial (bladder) cancer. Like other ADCs, the drug works by attaching a powerful targeted therapy to a targeted delivery agent, directing treatment where it is most needed. This drug targets NECTIN-4, a protein biomarker that is active in some solid tumor cancers including some breast cancers. Enfortumab vedotin is sometimes given with the immunotherapy drug pembrolizumab.

Results

The EV-202 phase II clinical trial tested enfortumab vedotin in 87 participants with locally advanced or metastatic breast cancer. Of these, 45 had hormone receptor-positive, HER2-negative breast cancer and 42 had triple-negative breast cancer. Everyone had undergone prior treatment with chemotherapy. Participants with hormone receptor-positive breast cancer also had been treated with endocrine therapy, with or without a CDK 4/6 inhibitor. Participants with triple-negative breast cancer had already tried immunotherapy. Most participants (69) in the trial had breast cancers that tested positive for NECTIN-4 even though a positive test was not required for eligibility.

The trial tracked how well the cancer responded to enfortumab vedotin. Seven (15.6%) of the participants with hormone receptor-positive, HER2-negative breast cancer saw some response. The triple-negative breast cancer group did slightly better (eight people or 19%). Yet these results did not meet the trial goals of 12 out of 40 responders in the hormone receptor-positive group and 10 out of 40 responders in the triple-negative breast cancer group.

The average time without cancer growing or spreading was 5.4 months for the hormone receptor-positive group and 3.5 months for the triple-negative breast cancer group. The level of NECTIN-4 in the tumor did not affect how well the drug worked.

Nearly everyone in the trial reported at least one side effect, with fatigue, itchiness, rash, and nausea being the most common. Commonly reported severe side effects were rash, itchiness, and liver test abnormalities. More than half of the participants paused or discontinued treatment at some point due to rash. Overall, however, the drug was safe and these side effects were manageable.

What does this mean for you?

These trial results are disappointing, but perhaps not the final word on enfortumab vedotin or NECTIN-4 as a target. The research team plans to look at other ways this drug, which has been effective in urothelial cancer, might be used in breast cancer.

“The enfortumab vedotin trial was done in a heavily pretreated patient population. Despite this, there were some responses to treatment, so it warrants further study. It is possible that when given earlier, it would be more effective,” says LBBC Medical Advisory Board member Rita Nanda, MD, director of the breast medical oncology program and associate professor of medicine at the University of Chicago.

Hear more from Dr. Nanda at our free June 13 webinar, Updates from the 2024 ASCO Annual Meeting.