Enfortumab Vedotin Demonstrates Long-Term Survival Benefits Among Patients With Advanced Urothelial Carcinoma

Enfortumab vedotin maintained clinically meaningful overall survival benefit at a median follow-up of approximately 2 years, compared with chemotherapy, among patients with advanced urothelial carcinoma who had been previously treated.

In the phase 3 EV-301 trial, 608 patients with locally advanced or metastatic urothelial carcinoma who had previously been treated with platinum-containing chemotherapy and had progressed during or after treatment with a PD-1/PD-L1 inhibitor were randomized to receive either enfortumab vedotin or chemotherapy. The primary end point was overall survival with secondary end points including progression-free survival (PFS), objective response, and safety.

Jonathan Rosenberg, MD, Memorial Sloan Kettering Cancer Center, New York, New York, and coauthors noted that, in the prespecified interim analysis of the trial, “enfortumab vedotin demonstrated OS and progression-free survival benefit versus investigator-preselected chemotherapy of docetaxel, paclitaxel, or vinflunine.”

The median follow-up duration was 23.75 months. For patients treated with enfortumab vedotin, risk of death was reduced by 30% compared with chemotherapy (hazard ratio [HR], 0.70; 95% confidence interval [CI], 0.58 to 0.85; 1-sided, log-rank P < .00015). Median PFS estimates were 5.55 months in the enfortumab vedotin arm and 3.71 months in the chemotherapy arm. The PFS was also improved with enfortumab vedotin compared with chemotherapy (HR 0.63; 95% CI, 0.53 to 0.76; 1-sided, log-rank P < .00001). The confirmed overall response rate was 41.32% in the enfortumab vedotin arm vs 18.58% in the chemotherapy arm. The disease control rate was 71.88% and 53.38%, respectively.

The rate of grade 3 adverse events was 52.4% in the enfortumab vedotin arm vs 50.5% in the chemotherapy arm. Authors also noted that “rates of all-grade [treatment related adverse events] in this long-term analysis were the same as in the interim/primary analysis.”

Dr Rosenberg et al concluded, “Continued survival benefits of enfortumab vedotin over chemotherapy in treated advanced urothelial carcinoma were shown” with “no new safety concerns…identified in the long-term follow-up.”

They also noted studies have been conducted and are ongoing to evaluate enfortumab vedotin in earlier treatment settings of urothelial carcinoma in combination with other agents, and as a monotherapy for other solid tumors.

Source:

Rosenberg JE, Powles T, Sonpavde GP, et al. EV301 long-term outcomes: 24 month findings from the phase III trial of enfortumab vedotin vs chemotherapy in patients with previously treated advanced urothelial carcinoma. Ann Oncol. Published online: September 6, 2023. doi:10.1016/j.annonc.2023.08.016