Real-world (rw) safety of first-line (1L) systemic regimens for locally advanced or metastatic urothelial cancer (la/mUC): Updated results from the ELEVATE UC-I study.

Abstract

680 Background: The rw safety of contemporary 1L treatment (tx) regimens for la/mUC has been previously reported. This updated analysis, including additional patients (pts) and an extended study period, provides a more comprehensive assessment of the incidence of rw tx-emergent adverse events (rwTEAEs). Methods: This retrospective cohort study identified adult pts diagnosed with la/mUC in the US from Jan 2020 to Jun 2024 using the Premier PINC AI Healthcare Database. Cohorts were based on 1L tx: enfortumab vedotin + pembrolizumab (EV + P), cisplatin- or carboplatin-based chemotherapy (± avelumab maintenance), and immune checkpoint inhibitor (ICI) monotherapy. To adjust for 1L tx exposure, rwTEAEs were calculated as the number of events per 1,000 person-days on tx. Analyses were descriptive. Results: 7,984 pts were included. Median age was 72 years (IQR, 64-78), 73% of pts were male, and 83% were White; mean Charlson-Deyo Comorbidity Index was 5.02 (SD, 3.40). Median follow-up was 140 days (IQR, 92-175). Most frequent rwTEAEs included infusion-related reactions (53%), anemia (33%), fatigue (20%), asthenia (20%), and nausea/vomiting (18%). Incidence of specific rwTEAEs of interest varied across 1L tx (Table). ICI monotherapy had the lowest overall rwTEAE rates, while platinum-based chemotherapies demonstrated higher rates of hematologic toxicities. EV + P had higher rates of fatigue, peripheral neuropathy, and rash. Conclusions: This expanded analysis from the ELEVATE UC-I study enhances understanding of the rw safety of contemporary 1L txs for la/mUC, highlighting distinct toxicity profiles. Findings may inform pt counseling, proactive mitigation of tx toxicity, and shared decision-making. Future research may further adjust rwTEAE estimates for clinicodemographic and disease characteristics and evaluate the associated healthcare resource utilization and economic impacts. Incidence of specific rwTEAEs of interest (rate per 1000-person days on tx) overall and by 1L tx regimen for la/mUC. 1L Tx Overall cohort(n=7,984) EV + P (n=343) Cisplatin-based chemo + avelumab (n=223) Cisplatin-based chemo alone (n=3,608) Carboplatin-based chemo + avelumab (n=201) Carboplatin-based chemo alone (n=1,250) ICI monotherapy (n=2,359) Median follow-up, days 140 147 298 139 278 112 154 Incidence rate (no. of events per 1,000 person-days on tx)  Fatigue 2.38 3.87 2.41 2.21 2.90 2.16 2.37  Neutropenia 2.05 0.54 3.11 3.45 2.41 3.70 0.20  Diarrhea 0.75 1.23 0.49 0.74 0.55 0.68 0.80  Chemotherapy-induced peripheral neuropathy 0.67 2.52 1.69 0.65 0.57 0.62 0.36  Decreased appetite 0.43 1.06 0.33 0.40 0.62 0.67 0.32  Rash 0.40 1.91 0.15 0.20 0.30 0.18 0.54  Hyperglycemia 0.23 0.37 0.63 0.23 0.31 0.21 0.14 Chemo, chemotherapy.