Primary results from the phase 3 EV-302 study in first-line locally advanced/metastatic urothelial cancer (la/mUC) demonstrated statistically significantly longer overall survival (OS) and progression-free survival (PFS) with enfortumab vedotin + pembrolizumab (EV+P) vs chemotherapy (chemo) in the overall population and improved outcomes in a post hoc analysis of patients from Asia. Based on these results, EV+P is considered the new standard of care for first-line la/mUC. In an updated analysis with ~2.5 years of median follow-up, EV+P continued to show superior efficacy vs chemo, consistent with the primary analysis. Here, we present updated results from the pan-Asian subgroup analysis.

This analysis included patients from China, Japan, South Korea, Singapore, Thailand and Taiwan. Eligible adult patients had unresectable Ia/mUC that was previously untreated with PD-(L)1 inhibitors or other systemic therapy. Patients were randomly assigned 1:1 to receive 3-week cycles of EV (IV 1.25 mg/kg on days 1 and 8) + P (IV 200 mg on day 1) or chemo (gemcitabine with cisplatin or carboplatin). Dual primary endpoints were PFS by blinded independent central review per Response Evaluation Criteria in Solid Tumors v1.1, and OS. Secondary endpoints included objective response rate (ORR) and safety.

From 886 patients randomized, 176 were enrolled in Asia and included in this analysis (EV+P, n=94; chemo, n=82). Patient characteristics were similar between arms and broadly similar to the overall population. At data cutoff (8 Aug 2024), median (95% CI) follow-up was 28.1 (26.5, 29.2) months. Median PFS was longer with EV+P (23.8 months) vs chemo (6.3 months) with a 63% decrease in the risk of progression or death (HR [95% CI]: 0.37 [0.24, 0.57]). Median OS was not estimable for EV+P vs 18.0 months for chemo, with a 67% decrease in the risk of death (HR [95% CI]: 0.33 [0.20, 0.54]). Confirmed ORR was 72.2% for EV+P vs 35.0% for chemo. Grade ≥3 TRAEs occurred in 66.0% and 68.4% of patients in the EV+P and chemo arms, respectively. Grade ≥3 TRAEs of special interest for EV included skin reactions (28.7%), hyperglycemia (10.6%) and peripheral neuropathy (8.5%); 13.8% and 5.3% of patients discontinued EV due to treatment-related peripheral neuropathy or skin reactions, respectively; none discontinued EV due to hyperglycemia. Grade ≥3 treatment-emergent AEs of special interest for P included severe skin reactions (18.1%) and pneumonitis (7.4%); 8.5% of patients discontinued P due to treatment-emergent pneumonitis; none discontinued P due to severe skin reactions.

In this updated analysis of the EV-302 pan-Asian subgroup, EV+P continues to demonstrate improved outcomes vs chemo in patients with previously untreated la/mUC. Durable efficacy results were consistent with those of the overall population. The safety profile of EV+P remained consistent with the primary analysis of this subgroup. These results further support EV+P as the first-line standard of care for la/mUC.