Enfortumab Vedotin Improves Survival Outcomes in Urothelial Cancer

Thomas Powles, MD, MBBS, MRCP, discusses the results of the phase 3 EV-301 trial for enfortumab vedotin in patients with urothelial cancer.

Thomas Powles, MD, MBBS, MRCP, a professor of genitourinary oncology, director of the Bart Cancer Centre, and lead for Solid Tumour Research at Cancer Research UK, discusses the results of the phase 3 EV-301 trial (NCT03474107) for enfortumab vedotin (Padcev) in patients with urothelial cancer.

The EV-301 study of patients with locally advanced or metastatic urothelial cancer led to an FDA approval of enfortumab in July 2021 after demonstrating survival benefit and tolerable safety profile.

EV-301 was a 1:1 randomized study of 608 patients who had previously received platinum-based chemotherapy and experienced disease progression during or after PD-1/PD-L1 treatment. They were administered either enfortumab vedotin or standard docetaxel, paclitaxel, or vinflunine chemotherapy. Enfortumab vedotin is an antibody-drug conjugate that targets Nectin-4, a cell adhesion molecule that is highly expressed in urothelial cancer.

The trial’s primary end point was overall survival (OS). After a follow-up of 11.1 months, the median OS was 12.9 months for those who received enfortumab vedotin compared with 9.0 months with chemotherapy—an increase of 3.9 months with a hazard ratio of 0.70. Overall response rate (ORR) for enfortumab vedotin was also significantly higher (40.6% vs 17.9%).

In terms of tolerability, the rate of treatment-related adverse events (TRAEs) was comparable in general. For serious TRAEs, patients who received enfortumab vedotin had a rate of serious TRAEs of 22.6% versus 23.4%, and grade 3 or higher TRAEs were around 50% in both groups. Certain TRAEs were more common in each group: maculo-papular rash in the group that received enfortumab vedotin and decreased neutrophil count and white blood cell count in the group that received chemotherapy.


0:08 | The EV-301 study is a large, randomized phase 3 study that incorporates patients who have progressed on platinum-based chemotherapy and immune checkpoint inhibitors. It's a 650-patient study, which is robust, and it showed a significant survival advantage for enfortumab vedotin versus chemotherapy. The chemotherapy choice was docetaxel, paclitaxel, or vinflunine, which are standard.

The hazard ratio was 0.70, which was statistically significant, showing a 30% reduction in the risk of death. OS in the enfortumab vendotin arm was approximately 13 months, which is long in this setting. The ORR was 40% versus 18%. The hazard ratio for PFS also favored enfortumab vendotin significantly, so the efficacy signal was consistent, and [that is] really important. And when we give this drug to my patients, this is reinforced. We see really great responses and patients’ pain reducing with therapy. So it's clearly a very active therapy in urothelial cancer.

People obviously asked, “Well, it's a new class of drug, what's the toxicity profile like?” The toxicity profile is manageable. In fact, in the adverse event profile, the percentage of grade 3 or 4 adverse events were about 50% in both groups.