Antibody-drug conjugate enfortumab vedotin prolongs survival of patients with metastatic urothelial carcinoma

This article from the NEJM meta-Journal (NEJM Journal Watch) Enfortumab Vedotin Improves Survival in Patients with Heavily Treated Metastatic Urothelial Cancerenfortumab vedotin prolong survival comment author has been heavily pre-treated patients with metastatic urothelial carcinoma: Robert Dreicer, MD, MS, MACP, FASCO In this phase 3 trial, all primary endpoints showed that enfortumab vedotin is more effective than chemotherapy.

For decades, we have made limited progress in the treatment of metastatic urothelial cancer, but in the past few years, a variety of new therapies have been approved by the US FDA.

Although still in a rapid development stage, the current standard treatment is platinum-based chemotherapy with checkpoint inhibitors (anti-PD-1/PD-L1) (the latter is used as maintenance therapy or used after the disease has progressed).

enfortumab vedotin (EV) is a monoclonal antibody-drug conjugate targeting connexin-4, which was initially approved by the FDA based on convincing phase 2 trial data.

Researchers have now published the results of an international phase 3 trial, which randomly assigned patients with platinum-based chemotherapy and PD-1 or PD-L1 inhibitor treatment to disease progression to receive EV therapy or chemotherapy (docetaxel, Paclitaxel or Vinflunine [vinflunine]).

The primary endpoint is overall survival.

Among the 608 patients included in this trial, the median age was 68 years, and 78% had visceral metastases.

The median duration of treatment in the EV and chemotherapy groups were 5 months and 3.
5 months, respectively.In the chemotherapy group, 229 patients were treated with a taxane drug, and 78 patients were treated with vinflunine.

During a median follow-up of 11.
1 months, all primary endpoints showed that the EV group was better than the chemotherapy group: the risk ratio of death (0.
70), longer overall survival (median, 12.
88 months vs.
8.
97 months), compared with High objective response rate (40.
6% vs.
17.
9%; P<0.
001) and low risk of progression or death (38% lower).

The incidence of grade 3 or higher adverse events in the two groups was 51.
4% and 49.
8%, respectively.

Comment on the results of this phase 3 trial confirming that enfortumab vedotin can play a role in patients with advanced urothelial cancer treated with platinum-based chemotherapy and checkpoint inhibitors.

In patients who received less treatment in the past, EV combined with anti-PD-1 drug pembrolizumab also showed interesting anti-cancer activity.

Phase 3 trials of the above-mentioned combination therapy are underway.

Commented articles Powles T et al.
Enfortumab vedotin in previously treated advanced urothelial carcinoma.
N Engl J Med 2021 Feb 12; [e-pub].
(https://doi.
org/10.
1056/NEJMoa2035807) NEJM journals collection NEJM journals collection (NEJM Journal Watch) is published by NEJM Group.
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