Enfortumab Vedotin Shows Meaningful, Sustained OS Benefit in Bladder Cancer

The global, open-label, phase 3 EV-301 study (NCT03474107) included patients who had been previously treated with platinum-containing chemotherapy and experienced disease progression on or following treatment with a PD-1/PD-L1 inhibitor.

Treatment with enfortumab vedotin-ejfv (Padcev) resulted in a clinically meaningful improvement in overall survival (OS) over chemotherapy in patients with locally advanced or metastatic urothelial carcinoma, according to findings from the phase 3 EV-301 study (NCT03474107) published in Annals of Oncology.

In a population of 608 patients who were treated with enfortumab vedotin (n = 301) or chemotherapy (n = 307), the risk of death decreased by 30% in the experimental arm (HR, 0.70; 95% CI, 0.58-0.85; P = .00015); the median follow-up was 23.75 months. The median OS estimates in each respective arm were 12.91 months (95% CI, 11.01-14.92) compared with 8.94 months (95% CI, 8.25-10.25).

Notably, investigators also reported an improvement in progression-free survival (PFS) with enfortumab vedotin compared with chemotherapy, as the risk of disease progression or death decreased by 37% in the experimental arm (HR, 0.63; 95% CI, 0.53-0.76; P <.00001). Additionally, the estimated median PFS was 5.55 months (95% CI, 5.32-6.28) in the enfortumab vedotin cohort vs 3.71 months (95% CI, 3.52-3.94) in the chemotherapy cohort.

The global, open-label study included patients who had been previously treated with platinum-containing chemotherapy and experienced disease progression on or following treatment with a PD-1/PD-L1 inhibitor. Patients were randomly assigned to receive treatment with either enfortumab vedotin at a dose of 1.25 mg/kg on days 1, 8, and 15 of every 28-day cycle or 75 mg/m² of docetaxel, 175 mg/m² of paclitaxel, or 320 mg/m² of vinflunine on day 1 of every 21-day cycle.

The study’s primary end point was OS, with key secondary end points including overall response rate (ORR), duration of response, and disease control rate (DCR).

At the study’s cutoff date of July 2021, a total of 444 deaths were reported, including 207 in the enfortumab vedotin arm and 237 in the chemotherapy arm. A total of 94.7% and 98.0% of patients in each respective arm discontinued treatment—most commonly due to disease progression. Additionally, 6% of patients in the chemotherapy arm crossed over to receive enfortumab vedotin.

The confirmed ORR was 41.32% (95% CI, 35.57%-47.25%) compared with 18.58% (95% CI, 14.32%-23.49%; P <.001) in the enfortumab vedotin arm and the chemotherapy arm, respectively. Additionally, the DCR in each respective cohort was 71.88% (95% CI, 66.30%-76.99%) vs 53.38% (95% CI, 47.52%-59.17%; P <.001). In total, 26.4% of responders in the enfortumab vedotin group and 19.1% in the chemotherapy group were alive and progression free at 24 months.

Treatment-related adverse effects (TRAEs) occurred in 93.9% vs 91.8% of patients in the experimental and control arms, respectively, and serious TRAEs occurred in 22.6% vs 23.4%. Additionally, high-grade TRAEs occurred in 52.4% vs 50.5% of patients in each respective cohort.

Frequent any-grade TRAEs in the enfortumab vedotin and chemotherapy cohorts, respectively, included alopecia (45.6% vs 37.1%), peripheral sensory neuropathy (34.8% vs 21.6%), pruritus (32.4% vs 4.8%), fatigue (31.4% vs 22.7%), and decreased appetite (31.1% vs 23.7%). Additionally high-grade toxicities in each respective arm consisted of maculopapular rash (7.4% vs 0.0%), fatigue (6.8% vs 4.5%), peripheral sensory neuropathy (5.1% vs 2.1%), decreased neutrophil count (6.1% vs 14.1%), and neutropenia (4.7% vs 6.2%).

Reference

Rosenberg JE, Powles T, Sonpavde GP, et al. EV-301 long-term outcomes: 24-month findings from the phase III trial of enfortumab vedotin versus chemotherapy in patients with previously treated advanced urothelial carcinoma. Ann Oncol. Published online September 6, 2023. doi:10.1016/j.annonc.2023.08.016