The phase 3 EV-301 trial compared the efficacy of enfortumab vedotin (EV) against chemotherapy in patients with previously treated locally advanced or metastatic urothelial carcinoma. An exploratory analysis recently evaluated the long-term findings of the study, with a median follow-up of approximately 2 years.
The study included 608 patients who previously experienced disease progression during or after PD-1/L1 inhibitor treatment. Patients were randomized to receive either EV or a chemotherapy treatment of docetaxel, paclitaxel, or vinflunine. A total of 301 patients received EV, while 307 underwent chemotherapy.
The primary end point was overall survival (OS), and secondary end points were progression-free survival (PFS), objective response, and safety. With a median follow-up of 23.75 months, 444 deaths occurred (EV n=207; chemotherapy n=237). The risk of death was reduced by 30% with EV versus chemotherapy (hazard ratio [HR], 0.70; 95% CI, 0.58-0.85; 1-sided, log-rank P=.00015), while PFS was also improved with EV (HR, 0.63; 95% CI, 0.53-0.76; 1-sided, log-rank P<.00001).
Adverse events (AEs) grade ≥3 occurred in 52.4% of patients treated with EV and 50.5% of patients treated with chemotherapy. Grade ≥3 treatment-related decreased neutrophil count (14.1% vs 6.1%), decreased white blood cell count (7.2% vs 1.4%), and anemia (7.9% vs 2.7%) were more common in patients treated with chemotherapy versus EV, while maculopapular rash (7.4% vs 0%), fatigue (6.8% vs 4.5%), and peripheral sensory neuropathy (5.1% vs 2.1%) were more common in patients treated with EV.
Other special interest AEs, such as treatment-related skin reactions, occurred in 47.3% of patients receiving EV and 15.8% of patients receiving chemotherapy; peripheral neuropathy occurred in 48.0% versus 31.6%, respectively, and hyperglycemia occurred in 6.8% versus 0.3%, respectively.
After a median follow-up of approximately 2 years, EV showed clinically meaningful OS benefit over chemotherapy, a result that was consistent with findings from the EV-301 primary analysis. PFS and overall response benefit remained consistent. AEs were manageable, and no new safety signals were observed.