Real-world time on treatment (rwTOT) with first-line (1L) enfortumab vedotin and pembrolizumab (EV+P) after U.S. Food and Drug Administration approval for advanced urothelial cancer (aUC).
Authors: Mayer Melanie , Seewald Nicholas , Perez Ernesto Ulloa , Homet Moreno Blanca , Ramamurthy Chethan , Babcock Aram , Li Haojie , Mamtani Ronac 
Published: February 2025

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Background:
EV+P received accelerated approval (AA) for cisplatin (cis)-ineligible aUC patients in April 2023 (EV-103) and full approval (FA) for all previously untreated patients in December 2023 (EV-302). In EV-302 trial, median durations of treatment with EV+P was 9.4 months (7.0 and 8.5 months for EV and P, respectively). We previously demonstrated high uptake of EV+P post AA in the real-world. Here, we examine rwToT with 1L EV+P with nearly 1 year of follow-up post-AA.
Methods:
This descriptive, post-marketing, retrospective cohort study used the Flatiron Health longitudinal database derived from EHR records of US patients with aUC initiating 1L EV+P after April 5, 2023 (AA) but before December 15, 2023 (FA). rwToT for EV+P was defined as length from first administration date of EV+P regimen to 1L therapy discontinuation, defined as last administration date of either component (i.e., EV or P) if patient initiated a next line of therapy, died during therapy, or had a gap of >60 days between last recorded dose and last contact date. rwToT was also estimated for each EV+P component. If no discontinuation criteria were met, the patient was censored at data cut-off (March 31, 2024). The Kaplan-Meier method was used for analysis of rwToT, including median rwToT (months) and 30-, 90-, 180-day on-treatment rates (%).
Results:
We identified 111 patients with aUC who initiated 1L EV+P after AA but before FA (mean age: 73.9 y, 75.7% male, 77.0% white, 23.7% ECOG performance status ≥2, 75.2% cis-ineligible, and 84.7% from community practices). As of March 31, 2024, approximately 41.4% (n=46) discontinued both EV and P; 9.9% [n=11] began subsequent therapy, 27.0% [n=30] died, and remaining patients were censored at end of follow-up (58.6%, n=65). Median rwToT (95% confidence interval [CI]) for EV+P, EV, and P were 8.2 months (6.5-not reached [NR]), 7.2 months (5.2-NR), and NR (6.3-NR), respectively (on-treatment rates reported in Table). Among 1L EV+P treated patients receiving subsequent therapies, 72.7% (9/11) received gemcitabine and carboplatin as the first subsequent therapy.
Conclusions:
In this large and predominantly cis-ineligible cohort of advanced urothelial cancer patients treated with EV+P in contemporary practice, rwTOT approximated duration of treatment in clinical trials. Most 1L EV+P users receiving subsequent anticancer therapy received platinum-based chemotherapy.

rwToT with 1L EV+P for patients with advanced urothelial cancer (N=111).

EV+P
EV
P

Discontinued, n (%)
46 (41.4)
52 (46.8)
47 (42.3)

Censored, n (%)
65 (58.6)
59 (53.2)
64 (57.7)

Median rwToT, months (95% CI)
8.1 (6.4-NR)
7.1 (5.1-NR)
NR (6.2-NR)

On-treatment rate, % (95%CI)

30-d
84.7(78.2, 91.7)
82.0(75.1, 89.5)
81.1(74.1, 88.7)

90-d
72.1(64.2, 80.9)
65.8(57.5, 75.2)
72.1(64.2, 80.9)

180-d
60.4(51.4, 70.9)
54.0(45.0, 64.9)
60.0(51.1, 70.4)