Enfortumab vedotin as a promising treatment option for bladder cancer: phase 3 results

New therapy prolongs survival in the 2^nd line for patients with urothelial carcinoma. Enfortumab vedotin may become the new standard of care for patients with previously treated locally advanced or metastatic urothelial carcinoma (la/mUC). In the recent phase 3 EV-301 trial, treatment with enfortumab vedotin resulted in prolonged overall survival (OS) rates in these patients compared with treatment with chemotherapy.

OS is poor in patients who have previously received platinum-based chemotherapy and checkpoint (PD-1/PD-L1) inhibitor therapy. Enfortumab vedotin is an antibody-drug conjugate approved by the FDA in 2019 that is directed against nectin-4, a molecule that is highly expressed in la/mUC.

Dr Thomas Powles (Barts Cancer Centre, UK) shared the results of the EV-301 trial (NCT03474107), an open-label, phase 3 trial comparing the OS of participants with la/mUC who were progressing during or after treatment with PD-1. They were randomised to receive either enfortumab vedotin or standard chemotherapy (i.e. docetaxel, vinflunine, or paclitaxel) [1,2]. Enrolled were 608 participants, of whom 301 were randomised to the enfortumab vedotin arm and the remaining 307 to the chemotherapy arm.

At 11.1 months follow-up, the primary endpoint of median OS was longer by 3.9 months in the enfortumab vedotin arm compared with the chemotherapy arm (12.9 vs 9.0 months; HR 0.70; 95% CI 0.56–0.89; 1-sided P=0.001). At the time of interim analysis, 301 deaths had occurred (49.5% of total number of participants). Of these deaths, 134 had occurred in the enfortumab vedotin group (44.5% of participants in this group) and 167 in the chemotherapy group (54.4% of this group).

Secondary endpoints included progression-free survival, objective response rate, and rate of adverse events. Progression-free survival in the enfortumab vedotin group was 5.6 months versus 3.7 months in the chemotherapy group (HR 0.61; 95% CI 0.50–0.75; 1-sided P<0.00001). Objective response rate was significantly superior in the enfortumab vedotin group compared with the chemotherapy group (40.6% vs 17.9%; 1-sided P<0.001). Adverse event rates were similar between groups (93.9% in the enfortumab vedotin group; 91.8% in the chemotherapy group).

Due to the superior OS achieved by patients with la/mUC treated with enfortumab vedotin together with its tolerable safety profile, Dr Powles recommended that enfortumab vedotin should become a new standard of care for this patient group.

1. Powles T. 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, ASCO Genitourinary Cancers Symposium, 11–13 February 2021.
2. Powles T, et al. N Engl J Med. 2021. DOI: 10.1056/NEJMoa2035807. Online ahead of print.

 

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Posted on 24 March, 202118 June, 2021