OBJECTIVES: Enfortumab vedotin+pembrolizumab (EV+P) is being evaluated as a first-line (1L) treatment in patients with locally advanced or metastatic urothelial carcinoma (la/mUC) in the ongoing, multi-cohort phase 1/2 study EV-103. As differing trial designs prevent indirect comparisons, we used simulation modeling to estimate the impact of maintenance avelumab (maintA) from the initiation of 1L therapy to contextualize outcomes with EV+P.

METHODS: A simulated cohort estimated median overall survival (mOS) from initiation of 1L gemcitabine+carboplatin (G/C)±maintA in cis-ineligible patients with la/mUC. The model estimated mOS in a maintA-ineligible simulated cohort, which was combined with the maintA-eligible cohort to yield an estimated mOS in the overall cis-ineligible population receiving G/C. Inputs were leveraged from published JAVELIN Bladder 100 and KEYNOTE-361 trial data. Results for maintA were compared descriptively to a simulated cohort given EV+P using a best curve fit of published EV-103 OS data. Sensitivity analyses varied the time frame for maintA eligibility (3.7-6.5 months) and proportions of patients eligible for and receiving maintA (75%-100%).

RESULTS: We estimated that 44% of the 1L modeled population treated with G/C were eligible for and received maintA and had mOS of 25.5 months based on JAVELIN trial results. The remaining patients (56%) were estimated to have mOS of 9.2 months for maintA-ineligible patients and 18.5 months for eligible but not receiving maintA. Combined, the estimated mOS, measured from initiation of 1L G/C, in the overall cis-ineligible cohort was 13.5 months. Sensitivity analyses varied mOS estimates for G/C±maintA from 13.2 to 14.6 months. Estimated mOS for EV+P was 26.5 months.

CONCLUSIONS: Our simulation model estimates that 1L EV+P may be associated with a longer mOS than 1L G/C±maintA in cis-ineligible patients with la/mUC. While this will need to be confirmed by ongoing trials, these data help to contextualize the potential role of EV+P in 1L la/mUC therapy.