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.
TRANSCRIPTION:
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.
Brain Cancer Awareness Month: Challenges and Innovations in Treatment
May 13th 2024In an interview with Targeted Oncology for Brain Cancer Awareness Month, Theodore Schwartz, MD, discussed the challenges of targeting brain tumors, emerging therapies, and strategies to overcome the blood-brain barrier.
Read More
Responders to UGN-101 Have Positive RFS in Upper Tract Urothelial Cancer
May 5th 2024In patients at 15 centers who had upper tract urothelial cancer, those with no evidence of disease after UGN-101 induction had a 68% rate of 3-year recurrence-free survival, and this outcome did not differ based on tumor status, method of instillation, or treatment intent.
Read More