As reported in The New England Journal of Medicine by Powles et al, a prespecified interim analysis of the phase III EV-301 trial has shown improved overall survival with enfortumab vedotin-ejfv vs investigator choice of chemotherapy in patients with previously treated advanced urothelial carcinoma.
Based on findings of durable objective responses in the phase II EV-201 trial, enfortumab vedotin was granted accelerated approval in December 2019 for the treatment of patients with locally advanced or metastatic urothelial cancer who have previously received a PD-1 or PD-L1 inhibitor and platinum-containing chemotherapy in the neoadjuvant/adjuvant, locally advanced, or metastatic setting.
In the open-label trial, 608 patients from sites in 19 countries who had received platinum-containing chemotherapy and had experienced disease progression during or after treatment with a PD-1 or PD-L1 inhibitor were randomly assigned to receive intravenous enfortumab vedotin at 1.25 mg/kg on days 1, 8, and 15 of 28-day cycles (n = 301) or chemotherapy selected by investigators before randomization (n = 307). Chemotherapy options consisted of docetaxel at 75 mg/kg (n = 117), paclitaxel at 175 mg/kg (n = 112), and vinflunine at 320 mg/m2 (n = 78) given on day 1 of 21-day cycles. The primary endpoint was overall survival in the intention-to-treat population.
At interim analysis (July 2020), with a median follow-up of 11.1 months, median overall survival was 12.88 months (95% confidence interval [CI] =10.58–15.21 months) in the enfortumab vedotin group vs 8.97 months (95% CI = 8.05–10.74 months) in the chemotherapy group (hazard ratio [HR] = 0.70, 95% CI = 0.56–0.89, P = .001). Survival rates at 12 months were 51.5% vs 39.2%. Hazard ratios favored enfortumab vedotin in nearly all subgroups examined, including those assessed according to chemotherapy regimen.
Median progression-free survival was 5.55 months (95% CI = 5.32–5.82 months) in the enfortumab vedotin group and 3.71 months (95% CI = 3.52–3.94 months) in the chemotherapy group (HR = 0.62, 95% CI = 0.51–0.75, P < .001). Among 288 vs 296 patients evaluable for response, an objective response was observed in 40.6% vs 17.9% of patients (P < .001), with complete response in 4.9% vs 2.7%. Median durations of response were 7.39 months vs 8.11 months. Disease control rates were 71.9% vs 53.4% (P < .001).
Treatment-related grade ≥ 3 adverse events occurred in 51.4% of patients in the enfortumab vedotin group vs 49.8% in the chemotherapy group. The most common were maculopapular rash (7.4%), fatigue (6.4%), and decreased neutrophil count (6.1%) in the enfortumab vedotin group and decreased neutrophil count (13.4%), anemia (7.6%), decreased white blood cell count (6.9%), neutropenia (6.2%), and febrile neutropenia (5.5%) in the chemotherapy group.
Treatment-related adverse events resulted in discontinuation of treatment in 13.5% vs 11.3% of patients, with the most common cause in the enfortumab vedotin group being peripheral neuropathy (2.4%). The most common treatment-related adverse events of special interest in the were rash (43.9% any grade, 14.5% grade ≥ 3 in the enfortumab vedotin group; 9.6% any grade, 0.3% grade 3 in chemotherapy group) and peripheral neuropathy (46.3% any grade, 3.7% grade 3 in the enfortumab vedotin group; 30.6% any grade, 2.4% grade 3 in the chemotherapy group).
The investigators concluded: “Enfortumab vedotin significantly prolonged survival as compared with standard chemotherapy in patients with locally advanced or metastatic urothelial carcinoma who had previously received platinum-based treatment and a PD-1 or PD-L1 inhibitor.”
Disclosure: The study was funded by Astellas Pharma US and Seagen. For full disclosures of the study authors, visit nejm.org.The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.