Real-World Data Support Enfortumab Vedotin for Urothelial Carcinoma Treatment

Enfortumab vedotin shows significant real-world benefits for patients with advanced urothelial carcinoma.

Real-world data from the EV-301 trial (NCT03474107) show that third-line enfortumab vedotin (Padcev; EV) significantly improved outcomes for patients with unresectable or metastatic urothelial carcinoma.¹

Findings from this multicenter retrospective study were presented at the ASCO 2025 Genitourinary Cancers Symposium.

“We aimed to investigate the efficacy and safety of EV in patients with unresectable or metastatic urothelial carcinoma in real-world practice,” investigators stated in a poster presented during the meeting. “The retrospective design is a limitation.”

In the study, 419 patients with unresectable or metastatic urothelial carcinoma received treatment from April 2004 to April 2024. Patients who received the following treatments were stratified into 3 treatment groups: first-line chemotherapy and sequential chemotherapy alone (chemo-alone group; n=87), maintenance or second-line immunotherapy after first-line chemotherapy (chemo/ICI group; n=217), and EV after first-line chemotherapy and immunotherapy (chemo/ICI/EV group; n=115).

The primary end point in the trial was the comparison of first-line progression-free survival (PFS) and overall survival (OS) between these 3 treatment groups and secondary end points focused on skin-related adverse events (AEs) regarding efficacy and safety in the chemo/ICI/EV group.

Results

Investigators noted that OS was significantly longer in the chemo/ICI/EV group; however, there was no significant difference in first-line PFS of first-line therapy between the 3 groups. The unadjusted OS from first-line therapy was 36 months in the chemo/ICI/EV group (P=.008), 25 months in the chemo/ICI group (P=.033), and 16 months in the chemo-alone group. Multivariable Cox regression analysis showed that the chemo/ICI/EV group was significantly associated with improved OS, according to the investigators.

Patient Characteristics

The average age in the chemo-alone group was 67 years (range, 23-84), 72 years (range, 31-93) in the chemo/ICI group and 74 years (range, 23-89) in the chemo/ICI/EV group and most patients were male: 73%, 78%, and 72%, respectively. Ten percent of patients in the chemo/ICI/EV group had a ECOG performance status greater than 1; this information was not documented for the other 2 groups.

There were 39% of patients with upper tract urothelial carcinoma (UTUC) in the chemo-alone group, 61% in the chemo/ICI group, and 45% in the chemo/ICI/EV group and percentages of those with T4 TNM staging were 16%, 32%, and 31%, respectively. Lymph node metastases were present in 70% in the chemo-alone group , 60% in the chemo/ICI group, and 47% in the chemo/ICI/EV group, and distant metastases were present in 76%, 67%, and 70%, respectively. In addition, liver metastases were present in 11%, 12%, and 13%, respectively.

Treatment History

In the chemo-alone group, 62% of patients received local therapy (54 underwent surgery, and none received radiation). In the chemo/ICI group, 53% of patients received local therapy (94 underwent surgery, and 18 received radiation). In the chemo/ICI/EV group, 59% of patients received local therapy (55 underwent surgery, and 13 received radiation).

Seventy-six percent of patients in the chemo-alone group received a first-line carboplatin-based regimen, compared with 64% in both the chemo/ICI and chemo/ICI/EV groups. In the chemo/ICI and chemo/ICI/EV groups, 21% of patients each received avelumab (Bavencio), and there were no patients who did in the chemo-alone group.

Skin-Related AEs

Investigators noted that patients with skin-related AEs (n=69) had significantly longer PFS and OS than those without (n=46). In addition, multivariable Cox regression analysis showed a significant association between skin-related AEs and prolonged relapse-free survival and OS.

The median PFS from EV treatment was 9.7 months for those with skin-related AEs and 5.9 months in those without (P=.001). The median OS from EV treatment was 19 months vs 14 months, respectively (P=.019). The number of cycles of EV treatment was 7 for those with skin-related AEs and 4 for those without (P=.001).

EV dose levels varied among patients, (0.75 mg/kg, 0.99mg/kg-0.75 mg/kg, 1.24-1.00 mg/kg, and 1.25 mg/kg) with the majority of patients with skin-related AEs receiving the 1.25 mg/kg dose in cycle 1. In contrast, the majority of patients without skin-related AEs received a dose of 1.25 mg/kg on cycle 10. However, overall patients without skin-related AEs received higher doses of EV throughout the 10 cycles of treatment whereas those with skin-related AEs had higher doses earlier on in the treatment course. Dose reductions occurred in 67% of patients with skin-related AEs and 35% in those without (P=.001)

Patient Characteristics Related to AEs

The average age of patients with and without skin-related AEs was 74 years and most patients were male (67% with skin-related AEs vs 80% without; P=.101). The body mass index for patients with skin-related AEs was 21.9 (range, 15.0-30.9) and 21.3 (range,14.4-29.2) for those without. Those with an ECOG performance score greater than 1 was 7% in those with skin-related AEs and 65% in those without (P<.001).

The percentage of those with UTUC and skin-related AEs was 49% and 39% in those without skin-related AEs. T4 TMN staging was observed in 30% vs 33%, lymph node metastases in 49% vs 50%, and distant metastases in 68% vs 72%, each respectively. In addition, liver metastases were observed in 13% of patients with skin-related AEs and without and 64% vs 76% had chronic kidney disease stage III, respectively.

Treatment History Related to AEs

Fifty-seven percent of patients with skin-related AEs had local therapy (32 patients had surgery and 7 received radiation) and 63% of patients without skin-related AEs (23 patients had surgery and 6 received radiation). Those receiving carboplatin-based regimens were 68% and 59%, respectively. There were 14% of patients with skin-related AEs who received prior avelumab and 77% who received prior pembrolizumab (Keytruda). This percentage was 30% and 74%, respectively, in those without skin-related AEs.

“Although skin AEs often led to dose reductions, dose adjustment of EV may be the key for long-term use and optimizing outcomes,” investigators stated.

Reference

Hatakeyama S, Ozaki K, Yamamoto H, et al Real-world analysis of the efficacy and safety of enfortumab vedotin in patients with locally advanced or metastatic urothelial carcinoma: A multicenter retrospective study. J Clin Oncol 43, 2025 (suppl 5; abstract 712). ASCO Genitourinary Cancers Symposium 2025.February 13-15, 2025, in San Francisco, California. doi:10.1200/JCO.2025.43.5_suppl.712