2020 ASCO GU | Urothelial Cancer: Preliminary Results of Phase III EV-301 Study Announced

On February 11-13, 2021, local time in the United States, the American Society of Clinical Oncology Annual Meeting of Urogenital Tumors (ASCO GU) was held online.

During the meeting, in the oral presentation session, the preliminary results of Phase III EV-301 research were announced! Background The survival rate of patients with locally advanced or metastatic urothelial cancer after treatment with platinum-containing chemotherapy and PD-1/PD-L1 inhibitors is low.

Nectin-4 protein is a cell adhesion molecule highly expressed in urothelial carcinoma.
Enfortumab vedotin (EV) is an antibody-drug conjugate targeting Nectin-4.

In the one-arm test, it was observed that EV has good anti-tumor activity.

The Phase III EV-301 study aims to further verify its clinical efficacy.

Methods: EV-301 is a global, open-label phase III clinical study, which aims to evaluate EV versus chemotherapy for locally advanced or metastatic urinary tracts with platinum-containing chemotherapy and PD-1/PD-L1 inhibitors.
Efficacy and safety of skin cancer.

The enrolled patients were randomly assigned to receive EV (1.
25 mg/kg, days 1, 8, and 15) or chemotherapy regimens selected by the investigator (docetaxel, paclitaxel, vinflunine) at a 1:1 ratio.

The primary endpoint is overall survival (OS), and the secondary endpoints include progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), safety and tolerability assessed by the investigator.

Results 608 cases of locally advanced or metastatic urothelial carcinoma were randomly assigned to receive EV (n=301) or chemotherapy (n=307).

As of July 15, 2020, the median follow-up time was 11.
1 months.
Compared with the chemotherapy group, EV can significantly prolong the median OS of patients by 3.
9 months.
The median OS of the two groups was 12.
9 months and 9.
0, respectively.
Months (HR=0.
7, P=0.
001).

In most subgroups, the benefit of OS in the EV group was observed.

The median PFS of the EV group and the chemotherapy group were 5.
6 months and 3.
7 months, respectively (HR=0.
61, P<0.
00001).

Compared with the chemotherapy group, the ORR and DCR of the EV group were also significantly higher.
The ORR of the EV group and the chemotherapy group were 40.
6% and 17.
9%, respectively (P<0.
001), and the DCR of the two groups were 71.
9% and 53.
4%, respectively (P <0.
001).

The incidence of treatment-related adverse events in the EV group and the chemotherapy group were 93.
9% and 91.
8%, respectively, and the serious treatment-related adverse events were 22.
6% and 23.
4%, respectively.

The incidence of treatment-related adverse events of grade ≥3 in both groups was ~50%.

Decreased neutropenia (13.
4%) and white blood cell count (6.
9%) were more common in the chemotherapy group, while papules (7.
4%) were more common in the EV group.

Conclusion In the treated patients with locally advanced or metastatic urothelial carcinoma, compared with standard chemotherapy, EV is the first targeted drug that shows OS benefit.

Based on the good clinical activity and acceptable safety of EV, researchers believe that EV can be used as the standard treatment for such patients.

Clinical trial information: NCT03474107.

Reference: Primary results of EV-301: A phase III trial of enfortumab vedotin versus chemotherapy in patients with previously treated locally advanced or metastatic urothelial carcinoma.
Abstract 393.
Oral session.